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Kanta Subbarao
The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia

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Journal article
Published: 23 August 2021 in JCI Insight
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The SARS-CoV-2 Receptor Binding Domain (RBD) is both the principal target of neutralizing antibodies, and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be implemented as a rapid surrogate assay for functional cell-based serological methods to measure the SARS-CoV-2 neutralising capacity of antibodies at the ACE2-RBD interface. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P and N501Y to the ACE2 receptor, and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research; informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.

ACS Style

Ester Lopez; Ebene R. Haycroft; Amy Adair; Francesca L. Mordant; Matthew T. O’Neill; Phillip Pymm; Samuel J. Redmond; Wen Shi Lee; Nicholas A. Gherardin; Adam K. Wheatley; Jennifer A. Juno; Kevin John Selva; Samantha K. Davis; Samantha L. Grimley; Leigh Harty; Damian F.J. Purcell; Kanta Subbarao; Dale I. Godfrey; Stephen J. Kent; Wai-Hong Tham; Amy W. Chung. Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay. JCI Insight 2021, 6, 1 .

AMA Style

Ester Lopez, Ebene R. Haycroft, Amy Adair, Francesca L. Mordant, Matthew T. O’Neill, Phillip Pymm, Samuel J. Redmond, Wen Shi Lee, Nicholas A. Gherardin, Adam K. Wheatley, Jennifer A. Juno, Kevin John Selva, Samantha K. Davis, Samantha L. Grimley, Leigh Harty, Damian F.J. Purcell, Kanta Subbarao, Dale I. Godfrey, Stephen J. Kent, Wai-Hong Tham, Amy W. Chung. Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay. JCI Insight. 2021; 6 (16):1.

Chicago/Turabian Style

Ester Lopez; Ebene R. Haycroft; Amy Adair; Francesca L. Mordant; Matthew T. O’Neill; Phillip Pymm; Samuel J. Redmond; Wen Shi Lee; Nicholas A. Gherardin; Adam K. Wheatley; Jennifer A. Juno; Kevin John Selva; Samantha K. Davis; Samantha L. Grimley; Leigh Harty; Damian F.J. Purcell; Kanta Subbarao; Dale I. Godfrey; Stephen J. Kent; Wai-Hong Tham; Amy W. Chung. 2021. "Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay." JCI Insight 6, no. 16: 1.

Brief report
Published: 16 August 2021 in Viruses
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The COVID-19 pandemic has highlighted the importance of understanding the immune response to seasonal human coronavirus (HCoV) infections such as HCoV-NL63, how existing neutralising antibodies to HCoV may modulate responses to SARS-CoV-2 infection, and the utility of seasonal HCoV as human challenge models. Therefore, in this study we quantified HCoV-NL63 neutralising antibody titres in a healthy adult population using plasma from 100 blood donors in Australia. A microneutralisation assay was performed with plasma diluted from 1:10 to 1:160 and tested with the HCoV-NL63 Amsterdam-1 strain. Neutralising antibodies were detected in 71% of the plasma samples, with a median geometric mean titre of 14. This titre was similar to those reported in convalescent sera taken from individuals 3–7 months following asymptomatic SARS-CoV-2 infection, and 2–3 years post-infection from symptomatic SARS-CoV-1 patients. HCoV-NL63 neutralising antibody titres decreased with increasing age (R2 = 0.042, p = 0.038), but did not differ by sex. Overall, this study demonstrates that neutralising antibody to HCoV-NL63 is detectable in approximately 71% of the healthy adult population of Australia. Similar titres did not impede the use of another seasonal human coronavirus (HCoV-229E) in a human challenge model, thus, HCoV-NL63 may be useful as a human challenge model for more pathogenic coronaviruses.

ACS Style

Sean A. Lynch; Kanta Subbarao; Siddhartha Mahanty; Bridget E. Barber; Eileen V. Roulis; Lia van der Hoek; James S. McCarthy; Kirsten M. Spann. Prevalence of Neutralising Antibodies to HCoV-NL63 in Healthy Adults in Australia. Viruses 2021, 13, 1618 .

AMA Style

Sean A. Lynch, Kanta Subbarao, Siddhartha Mahanty, Bridget E. Barber, Eileen V. Roulis, Lia van der Hoek, James S. McCarthy, Kirsten M. Spann. Prevalence of Neutralising Antibodies to HCoV-NL63 in Healthy Adults in Australia. Viruses. 2021; 13 (8):1618.

Chicago/Turabian Style

Sean A. Lynch; Kanta Subbarao; Siddhartha Mahanty; Bridget E. Barber; Eileen V. Roulis; Lia van der Hoek; James S. McCarthy; Kirsten M. Spann. 2021. "Prevalence of Neutralising Antibodies to HCoV-NL63 in Healthy Adults in Australia." Viruses 13, no. 8: 1618.

Journal article
Published: 07 July 2021 in Journal of Clinical Virology
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Influenza viruses must be amplified in cell culture for detailed antigenic analysis and for phenotypic assays assessing susceptibility to antiviral drugs or for other assays. Following on from the first external quality assessment (EQA) for isolation and identification of influenza viruses using cell culture techniques in 2016, a follow up EQA was performed in 2019 for National Influenza Centres (NICs) in the World Health Organization (WHO) South East Asia and Western Pacific Regions. Nineteen WHO NICs performed influenza virus isolation and identification techniques on an EQA panel comprising 16 samples, containing influenza A or B viruses and negative control samples. One sample was used exclusively to assess capacity to measure a hemagglutination titer and the other 15 samples were used for virus isolation and subsequent identification. Virus isolation from EQA samples was generally detected by assessment of cytopathic effect and/or hemagglutination assay while virus identification was determined by real time RT-PCR, hemagglutination inhibition and/or immunofluorescence assays. For virus isolation from EQA samples, 6/19 participating laboratories obtained 15/15 correct results in the first EQA (2016) compared to 11/19 in the follow up (2019). For virus identification in isolates derived from EQA samples, 6/19 laboratories obtained 15/15 correct results in 2016 compared to 13/19 in 2019. Overall, NIC laboratories in the Asia Pacific Region showed a significant improvement between 2016 and 2019 in terms of the correct results reported for isolation from EQA samples and identification of virus in isolates derived from EQA samples (p=0.01 and p=0.02, respectively).

ACS Style

Vivian K.Y. Leung; Yi-Mo Deng; Angela Todd; Heidi Peck; Iwona Buettner; Tasoula Zakis; Kanta Subbarao; Ian G. Barr; Karen Nahapetyan; Francis Y. Inbanathan; Magdi Samaan; Patrick C. Reading. A second external quality assessment of isolation and identification of influenza viruses in cell culture in the Asia Pacific region highlights improved performance by participating laboratories. Journal of Clinical Virology 2021, 142, 104907 .

AMA Style

Vivian K.Y. Leung, Yi-Mo Deng, Angela Todd, Heidi Peck, Iwona Buettner, Tasoula Zakis, Kanta Subbarao, Ian G. Barr, Karen Nahapetyan, Francis Y. Inbanathan, Magdi Samaan, Patrick C. Reading. A second external quality assessment of isolation and identification of influenza viruses in cell culture in the Asia Pacific region highlights improved performance by participating laboratories. Journal of Clinical Virology. 2021; 142 ():104907.

Chicago/Turabian Style

Vivian K.Y. Leung; Yi-Mo Deng; Angela Todd; Heidi Peck; Iwona Buettner; Tasoula Zakis; Kanta Subbarao; Ian G. Barr; Karen Nahapetyan; Francis Y. Inbanathan; Magdi Samaan; Patrick C. Reading. 2021. "A second external quality assessment of isolation and identification of influenza viruses in cell culture in the Asia Pacific region highlights improved performance by participating laboratories." Journal of Clinical Virology 142, no. : 104907.

Review
Published: 01 July 2021 in Cell Host & Microbe
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Summary The rapid and remarkably successful development, manufacture, and deployment of several effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is now tempered by three key challenges. First, reducing virus transmission will require prevention of asymptomatic and mild infections in addition to severe symptomatic infections. Second, the emergence of variants of concern with mutations in the S protein's receptor binding domain increases the likelihood that vaccines will have to be updated because some of these mutations render variants less optimally targeted by current vaccines. This will require coordinated global SARS-CoV-2 surveillance to link genotypes to phenotypes, potentially using the WHO's global influenza surveillance program as a guide. Third, concerns about the longevity of vaccine-induced immunity highlight the potential need for re-vaccination, depending on the extent to which the virus has been controlled and whether re-vaccination can target those at greatest risk of severe illness. Fortunately, as I discuss in this review, these challenges can be addressed.

ACS Style

Kanta Subbarao. The success of SARS-CoV-2 vaccines and challenges ahead. Cell Host & Microbe 2021, 29, 1111 -1123.

AMA Style

Kanta Subbarao. The success of SARS-CoV-2 vaccines and challenges ahead. Cell Host & Microbe. 2021; 29 (7):1111-1123.

Chicago/Turabian Style

Kanta Subbarao. 2021. "The success of SARS-CoV-2 vaccines and challenges ahead." Cell Host & Microbe 29, no. 7: 1111-1123.

Journal article
Published: 23 April 2021 in Proceedings of the National Academy of Sciences
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Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 104-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.

ACS Style

Phillip Pymm; Amy Adair; Li-Jin Chan; James P. Cooney; Francesca L. Mordant; Cody C. Allison; Ester Lopez; Ebene R. Haycroft; Matthew T. O’Neill; Li Lynn Tan; Melanie H. Dietrich; Damien Drew; Marcel Doerflinger; Michael A. Dengler; Nichollas E. Scott; Adam K. Wheatley; Nicholas A. Gherardin; Hariprasad Venugopal; Deborah Cromer; Miles P. Davenport; Raelene Pickering; Dale I. Godfrey; Damian F. J. Purcell; Stephen J. Kent; Amy W. Chung; Kanta Subbarao; Marc Pellegrini; Alisa Glukhova; Wai-Hong Tham. Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice. Proceedings of the National Academy of Sciences 2021, 118, 1 .

AMA Style

Phillip Pymm, Amy Adair, Li-Jin Chan, James P. Cooney, Francesca L. Mordant, Cody C. Allison, Ester Lopez, Ebene R. Haycroft, Matthew T. O’Neill, Li Lynn Tan, Melanie H. Dietrich, Damien Drew, Marcel Doerflinger, Michael A. Dengler, Nichollas E. Scott, Adam K. Wheatley, Nicholas A. Gherardin, Hariprasad Venugopal, Deborah Cromer, Miles P. Davenport, Raelene Pickering, Dale I. Godfrey, Damian F. J. Purcell, Stephen J. Kent, Amy W. Chung, Kanta Subbarao, Marc Pellegrini, Alisa Glukhova, Wai-Hong Tham. Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice. Proceedings of the National Academy of Sciences. 2021; 118 (19):1.

Chicago/Turabian Style

Phillip Pymm; Amy Adair; Li-Jin Chan; James P. Cooney; Francesca L. Mordant; Cody C. Allison; Ester Lopez; Ebene R. Haycroft; Matthew T. O’Neill; Li Lynn Tan; Melanie H. Dietrich; Damien Drew; Marcel Doerflinger; Michael A. Dengler; Nichollas E. Scott; Adam K. Wheatley; Nicholas A. Gherardin; Hariprasad Venugopal; Deborah Cromer; Miles P. Davenport; Raelene Pickering; Dale I. Godfrey; Damian F. J. Purcell; Stephen J. Kent; Amy W. Chung; Kanta Subbarao; Marc Pellegrini; Alisa Glukhova; Wai-Hong Tham. 2021. "Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice." Proceedings of the National Academy of Sciences 118, no. 19: 1.

Journal article
Published: 22 April 2021 in Cell Reports
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Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses subgenomic RNA (sgRNA) to produce viral proteins for replication and immune evasion. We apply long-read RNA and cDNA sequencing to in vitro human and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA upregulates earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of open reading frame 1ab (ORF1ab) containing nsp1 joins to ORF10, and the 3′ untranslated region (UTR) upregulates at 48 h post-infection in human cell lines. We identify double-junction sgRNA containing both TRS-dependent and -independent junctions. We find multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA and that sgRNA modifications are stable across transcript clusters, host cells, and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle.

ACS Style

Jessie J.-Y. Chang; Daniel Rawlinson; Miranda E. Pitt; George Taiaroa; Josie Gleeson; Chenxi Zhou; Francesca L. Mordant; Ricardo De Paoli-Iseppi; Leon Caly; Damian F.J. Purcell; Timothy P. Stinear; Sarah L. Londrigan; Michael B. Clark; Deborah A. Williamson; Kanta Subbarao; Lachlan J.M. Coin. Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection. Cell Reports 2021, 35, 109108 .

AMA Style

Jessie J.-Y. Chang, Daniel Rawlinson, Miranda E. Pitt, George Taiaroa, Josie Gleeson, Chenxi Zhou, Francesca L. Mordant, Ricardo De Paoli-Iseppi, Leon Caly, Damian F.J. Purcell, Timothy P. Stinear, Sarah L. Londrigan, Michael B. Clark, Deborah A. Williamson, Kanta Subbarao, Lachlan J.M. Coin. Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection. Cell Reports. 2021; 35 (6):109108.

Chicago/Turabian Style

Jessie J.-Y. Chang; Daniel Rawlinson; Miranda E. Pitt; George Taiaroa; Josie Gleeson; Chenxi Zhou; Francesca L. Mordant; Ricardo De Paoli-Iseppi; Leon Caly; Damian F.J. Purcell; Timothy P. Stinear; Sarah L. Londrigan; Michael B. Clark; Deborah A. Williamson; Kanta Subbarao; Lachlan J.M. Coin. 2021. "Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection." Cell Reports 35, no. 6: 109108.

Preprint content
Published: 07 April 2021
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Children have lower hospitalisation and mortality rates for coronavirus disease-2019 (COVID-19) than adults; however, younger children (<4 years of age)1 may develop more severe disease than older children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterized. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19. Systemic cellular and cytokine profiling showed initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8+ T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4+T (but not CD8+T) cells occurred over time, with predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Significant in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory.

ACS Style

Paul Licciardi; Danielle Wurzel; Melanie Neeland; Jeremy Anderson; Yara-Natalie Abo; Lien Anh Ha Do; Celeste Donato; Julie Bines; Zheng Quan Toh; Rachel Higgins; Sedi Jalali; Theresa Cole; Kanta Subbarao; Alissa McMinn; Kate Dohle; Gabrielle Haeusler; Sarah McNab; Annette Alafaci; Isabella Overmars; Vanessa Clifford; Lai-Yang Lee; Andrew Daly; Jim Buttery; Penelope Bryant; David Burgner; Andrew Steer; Shidan Tosif; Igor Konstantinov; Trevor Duke; Dan Pellicci; Nigel Crawford. Immune Responses in an Infant with Congenital Heart Disease and Severe COVID-19 . 2021, 1 .

AMA Style

Paul Licciardi, Danielle Wurzel, Melanie Neeland, Jeremy Anderson, Yara-Natalie Abo, Lien Anh Ha Do, Celeste Donato, Julie Bines, Zheng Quan Toh, Rachel Higgins, Sedi Jalali, Theresa Cole, Kanta Subbarao, Alissa McMinn, Kate Dohle, Gabrielle Haeusler, Sarah McNab, Annette Alafaci, Isabella Overmars, Vanessa Clifford, Lai-Yang Lee, Andrew Daly, Jim Buttery, Penelope Bryant, David Burgner, Andrew Steer, Shidan Tosif, Igor Konstantinov, Trevor Duke, Dan Pellicci, Nigel Crawford. Immune Responses in an Infant with Congenital Heart Disease and Severe COVID-19 . . 2021; ():1.

Chicago/Turabian Style

Paul Licciardi; Danielle Wurzel; Melanie Neeland; Jeremy Anderson; Yara-Natalie Abo; Lien Anh Ha Do; Celeste Donato; Julie Bines; Zheng Quan Toh; Rachel Higgins; Sedi Jalali; Theresa Cole; Kanta Subbarao; Alissa McMinn; Kate Dohle; Gabrielle Haeusler; Sarah McNab; Annette Alafaci; Isabella Overmars; Vanessa Clifford; Lai-Yang Lee; Andrew Daly; Jim Buttery; Penelope Bryant; David Burgner; Andrew Steer; Shidan Tosif; Igor Konstantinov; Trevor Duke; Dan Pellicci; Nigel Crawford. 2021. "Immune Responses in an Infant with Congenital Heart Disease and Severe COVID-19 ." , no. : 1.

Preprint content
Published: 11 March 2021
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Both previous infection and vaccination have been shown to provide potent protection from COVID-19. However, there are concerns that waning immunity and viral variation may lead to a loss of protection over time. Predictive models of immune protection are urgently needed to identify immune correlates of protection to assist in the future deployment of vaccines. To address this, we modelled the relationship between in vitro neutralisation levels and observed protection from SARS-CoV-2 infection using data from seven current vaccines as well as convalescent cohorts. Here we show that neutralisation level is highly predictive of immune protection. The 50% protective neutralisation level was estimated to be approximately 20% of the average convalescent level (95% CI = 14-28%). The estimated neutralisation level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level (CI = 0.7-13%, p = 0.0004). Given the relationship between in vitro neutralization titer and protection, we then used this to investigate how waning immunity and antigenic variation might affect vaccine efficacy. We found that the decay of neutralising titre in vaccinated subjects over the first 3-4 months after vaccination was at least as rapid as the decay observed in convalescent subjects. Modelling the decay of neutralisation titre over the first 250 days after immunisation predicts a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralisation titres against some SARS-CoV-2 variants of concern are reduced compared to the vaccine strain and our model predicts the relationship between neutralisation and efficacy against viral variants. Our analyses provide an evidence-based prediction of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

ACS Style

David S Khoury; Deborah Cromer; Arnold Reynaldi; Timothy E Schlub; Adam K Wheatley; Jennifer A Juno; Kanta Subbarao; Stephen J Kent; James A Triccas; Miles P Davenport. What level of neutralising antibody protects from COVID-19? 2021, 1 .

AMA Style

David S Khoury, Deborah Cromer, Arnold Reynaldi, Timothy E Schlub, Adam K Wheatley, Jennifer A Juno, Kanta Subbarao, Stephen J Kent, James A Triccas, Miles P Davenport. What level of neutralising antibody protects from COVID-19? . 2021; ():1.

Chicago/Turabian Style

David S Khoury; Deborah Cromer; Arnold Reynaldi; Timothy E Schlub; Adam K Wheatley; Jennifer A Juno; Kanta Subbarao; Stephen J Kent; James A Triccas; Miles P Davenport. 2021. "What level of neutralising antibody protects from COVID-19?" , no. : 1.

Journal article
Published: 03 March 2021 in Nature Communications
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SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.

ACS Style

Hyon-Xhi Tan; Jennifer A. Juno; Wen Shi Lee; Isaac Barber-Axthelm; Hannah G. Kelly; Kathleen M. Wragg; Robyn Esterbauer; Thakshila Amarasena; Francesca L. Mordant; Kanta Subbarao; Stephen J. Kent; Adam K. Wheatley. Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques. Nature Communications 2021, 12, 1 -10.

AMA Style

Hyon-Xhi Tan, Jennifer A. Juno, Wen Shi Lee, Isaac Barber-Axthelm, Hannah G. Kelly, Kathleen M. Wragg, Robyn Esterbauer, Thakshila Amarasena, Francesca L. Mordant, Kanta Subbarao, Stephen J. Kent, Adam K. Wheatley. Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques. Nature Communications. 2021; 12 (1):1-10.

Chicago/Turabian Style

Hyon-Xhi Tan; Jennifer A. Juno; Wen Shi Lee; Isaac Barber-Axthelm; Hannah G. Kelly; Kathleen M. Wragg; Robyn Esterbauer; Thakshila Amarasena; Francesca L. Mordant; Kanta Subbarao; Stephen J. Kent; Adam K. Wheatley. 2021. "Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques." Nature Communications 12, no. 1: 1-10.

Journal article
Published: 19 February 2021 in Nature Communications
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The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

ACS Style

Adam K. Wheatley; Jennifer A. Juno; Jing J. Wang; Kevin J. Selva; Arnold Reynaldi; Hyon-Xhi Tan; Wen Shi Lee; Kathleen M. Wragg; Hannah G. Kelly; Robyn Esterbauer; Samantha K. Davis; Helen E. Kent; Francesca L. Mordant; Timothy E. Schlub; David L. Gordon; David S. Khoury; Kanta Subbarao; Deborah Cromer; Tom P. Gordon; Amy W. Chung; Miles P. Davenport; Stephen J. Kent. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nature Communications 2021, 12, 1 -11.

AMA Style

Adam K. Wheatley, Jennifer A. Juno, Jing J. Wang, Kevin J. Selva, Arnold Reynaldi, Hyon-Xhi Tan, Wen Shi Lee, Kathleen M. Wragg, Hannah G. Kelly, Robyn Esterbauer, Samantha K. Davis, Helen E. Kent, Francesca L. Mordant, Timothy E. Schlub, David L. Gordon, David S. Khoury, Kanta Subbarao, Deborah Cromer, Tom P. Gordon, Amy W. Chung, Miles P. Davenport, Stephen J. Kent. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nature Communications. 2021; 12 (1):1-11.

Chicago/Turabian Style

Adam K. Wheatley; Jennifer A. Juno; Jing J. Wang; Kevin J. Selva; Arnold Reynaldi; Hyon-Xhi Tan; Wen Shi Lee; Kathleen M. Wragg; Hannah G. Kelly; Robyn Esterbauer; Samantha K. Davis; Helen E. Kent; Francesca L. Mordant; Timothy E. Schlub; David L. Gordon; David S. Khoury; Kanta Subbarao; Deborah Cromer; Tom P. Gordon; Amy W. Chung; Miles P. Davenport; Stephen J. Kent. 2021. "Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19." Nature Communications 12, no. 1: 1-11.

Research article
Published: 01 January 2021 in Microbiology Australia
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Since 2002, three zoonotic coronaviruses (CoV), SARS-CoV, MERS-CoV and SARS-CoV-2 have emerged in humans, establishing that emergence of coronaviruses from animal reservoirs represents a significant pandemic threat. SARS-CoV and MERS-CoV led to smaller epidemics with very high case fatality rates while SARS-CoV-2 resulted in a global pandemic. These zoonotic coronaviruses have their likely origins in bat species and they transmit to humans through intermediate hosts. Coronaviruses can occasionally jump between host species due to their high rate of recombination. Pandemic preparedness requires surveillance in animals and occupationally exposed humans and prevention and treatment strategies that have broad activity against coronaviruses.

ACS Style

Matthew J Gartner; Kanta Subbarao. The threat of zoonotic coronaviruses. Microbiology Australia 2021, 42, 4 .

AMA Style

Matthew J Gartner, Kanta Subbarao. The threat of zoonotic coronaviruses. Microbiology Australia. 2021; 42 (1):4.

Chicago/Turabian Style

Matthew J Gartner; Kanta Subbarao. 2021. "The threat of zoonotic coronaviruses." Microbiology Australia 42, no. 1: 4.

Preprint content
Published: 22 December 2020
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SummarySARS-CoV-2 uses subgenomic (sg)RNA to produce viral proteins for replication and immune evasion. We applied long-read RNA and cDNA sequencing to in vitro human and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA was upregulated earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of ORF1ab containing nsp1 joined to ORF10 and 3’UTR was upregulated at 48 hours post infection in human cell lines. We identified double-junction sgRNA containing both TRS-dependent and independent junctions. We found multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA, and that sgRNA modifications are stable across transcript clusters, host cells and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle. Our results are available via an interactive web-app at http://coinlab.mdhs.unimelb.edu.au/.

ACS Style

Jessie J.-Y. Chang; Daniel Rawlinson; Miranda E. Pitt; George Taiaroa; Josie Gleeson; Chenxi Zhou; Francesca L. Mordant; Ricardo De Paoli-Iseppi; Leon Caly; Damian F.J. Purcell; Tim P. Stinear; Sarah L. Londrigan; Michael B. Clark; Deborah A. Williamson; Kanta Subbarao; Lachlan J.M. Coin. Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection. 2020, 1 .

AMA Style

Jessie J.-Y. Chang, Daniel Rawlinson, Miranda E. Pitt, George Taiaroa, Josie Gleeson, Chenxi Zhou, Francesca L. Mordant, Ricardo De Paoli-Iseppi, Leon Caly, Damian F.J. Purcell, Tim P. Stinear, Sarah L. Londrigan, Michael B. Clark, Deborah A. Williamson, Kanta Subbarao, Lachlan J.M. Coin. Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection. . 2020; ():1.

Chicago/Turabian Style

Jessie J.-Y. Chang; Daniel Rawlinson; Miranda E. Pitt; George Taiaroa; Josie Gleeson; Chenxi Zhou; Francesca L. Mordant; Ricardo De Paoli-Iseppi; Leon Caly; Damian F.J. Purcell; Tim P. Stinear; Sarah L. Londrigan; Michael B. Clark; Deborah A. Williamson; Kanta Subbarao; Lachlan J.M. Coin. 2020. "Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection." , no. : 1.

Journal article
Published: 11 November 2020 in Nature Communications
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Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

ACS Style

Shidan Tosif; Melanie R. Neeland; Philip Sutton; Paul V. Licciardi; Sohinee Sarkar; Kevin J. Selva; Lien Anh Ha Do; Celeste Donato; Zheng Quan Toh; Rachel Higgins; Carolien Van De Sandt; Melissa M. Lemke; Christina Y. Lee; Suzanne K. Shoffner; Katie L. Flanagan; Kelly B. Arnold; Francesca L. Mordant; Kim Mulholland; Julie Bines; Kate Dohle; Daniel G. Pellicci; Nigel Curtis; Sarah McNab; Andrew Steer; Richard Saffery; Kanta Subbarao; Amy W. Chung; Katherine Kedzierska; David P. Burgner; Nigel W. Crawford. Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19. Nature Communications 2020, 11, 1 -8.

AMA Style

Shidan Tosif, Melanie R. Neeland, Philip Sutton, Paul V. Licciardi, Sohinee Sarkar, Kevin J. Selva, Lien Anh Ha Do, Celeste Donato, Zheng Quan Toh, Rachel Higgins, Carolien Van De Sandt, Melissa M. Lemke, Christina Y. Lee, Suzanne K. Shoffner, Katie L. Flanagan, Kelly B. Arnold, Francesca L. Mordant, Kim Mulholland, Julie Bines, Kate Dohle, Daniel G. Pellicci, Nigel Curtis, Sarah McNab, Andrew Steer, Richard Saffery, Kanta Subbarao, Amy W. Chung, Katherine Kedzierska, David P. Burgner, Nigel W. Crawford. Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19. Nature Communications. 2020; 11 (1):1-8.

Chicago/Turabian Style

Shidan Tosif; Melanie R. Neeland; Philip Sutton; Paul V. Licciardi; Sohinee Sarkar; Kevin J. Selva; Lien Anh Ha Do; Celeste Donato; Zheng Quan Toh; Rachel Higgins; Carolien Van De Sandt; Melissa M. Lemke; Christina Y. Lee; Suzanne K. Shoffner; Katie L. Flanagan; Kelly B. Arnold; Francesca L. Mordant; Kim Mulholland; Julie Bines; Kate Dohle; Daniel G. Pellicci; Nigel Curtis; Sarah McNab; Andrew Steer; Richard Saffery; Kanta Subbarao; Amy W. Chung; Katherine Kedzierska; David P. Burgner; Nigel W. Crawford. 2020. "Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19." Nature Communications 11, no. 1: 1-8.

Review article
Published: 02 November 2020 in Nature Reviews Immunology
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The rapid scale-up of research on coronavirus disease 2019 (COVID-19) has spawned a large number of potential vaccines and immunotherapies, accompanied by a commensurately large number of in vitro assays and in vivo models to measure their effectiveness. These assays broadly have the same end-goal - to predict the clinical efficacy of prophylactic and therapeutic interventions in humans. However, the apparent potency of different interventions can vary considerably between assays and animal models, leading to very different predictions of clinical efficacy. Complete harmonization of experimental methods may be intractable at the current pace of research. However, here we analyse a selection of existing assays for measuring antibody-mediated virus neutralization and animal models of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a framework for comparing results between studies and reconciling observed differences in the effects of interventions. Finally, we propose how we might optimize these assays for better comparison of results from in vitro and animal studies to accelerate progress.

ACS Style

David S. Khoury; Adam K. Wheatley; Mitchell D. Ramuta; Arnold Reynaldi; Deborah Cromer; Kanta Subbarao; David H. O’Connor; Stephen J. Kent; Miles P. Davenport. Measuring immunity to SARS-CoV-2 infection: comparing assays and animal models. Nature Reviews Immunology 2020, 20, 727 -738.

AMA Style

David S. Khoury, Adam K. Wheatley, Mitchell D. Ramuta, Arnold Reynaldi, Deborah Cromer, Kanta Subbarao, David H. O’Connor, Stephen J. Kent, Miles P. Davenport. Measuring immunity to SARS-CoV-2 infection: comparing assays and animal models. Nature Reviews Immunology. 2020; 20 (12):727-738.

Chicago/Turabian Style

David S. Khoury; Adam K. Wheatley; Mitchell D. Ramuta; Arnold Reynaldi; Deborah Cromer; Kanta Subbarao; David H. O’Connor; Stephen J. Kent; Miles P. Davenport. 2020. "Measuring immunity to SARS-CoV-2 infection: comparing assays and animal models." Nature Reviews Immunology 20, no. 12: 727-738.

Preprint content
Published: 01 October 2020
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Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace with more than 30 candidate vaccines now in clinical evaluation. Here we describe the preclinical development of an adjuvanted, prefusion-stabilised Spike (S) protein “Sclamp” subunit vaccine, from rational antigen design through to assessing manufacturability and vaccine efficacy. In mice, the vaccine candidate elicits high levels of neutralising antibodies to epitopes both within and outside the receptor binding domain (RBD) of S, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells. We also show protection in Syrian hamsters, which has emerged as a robust animal model for pulmonary SARS-CoV-2 infection. No evidence of vaccine enhanced disease was observed in animal challenge studies and pre-clinical safety was further demonstrated in a GLP toxicology study in rats. The Sclamp vaccine candidate is currently progressing rapidly through clinical evaluation in parallel with large-scale manufacture for pivotal efficacy trials and potential widespread distribution.

ACS Style

Daniel Watterson; Danushka Wijesundara; Naphak Modhiran; Francesca Mordant; Zheyi Li; Michael Avumegah; Christopher McMillan; Julia Lackenby; Kate Guilfoyle; Geert van Amerongen; Koert Stittelaar; Stacey Cheung; Summa Bibby; Mallory Daleris; Kym Hoger; Marianne Gillard; Eve Radunz; Martina Jones; Karen Hughes; Ben Hughes; Justin Goh; David Edwards; Judith Scoble; Lesley Pearce; Lukasz Kowalczyk; Tram Phan; Mylinh La; Louis Lu; Tam Pham; Qi Zhou; David Brockman; Sherry Morgan; Cora Lau; Mai Tran; Peter Tapley; Fernando Villalon Letelier; James Barnes; Andrew Young; Noushin Jaberolansar; Connor Scott; Ariel Isaacs; Alberto Amarilla; Alexander Khromykh; Patrick Reading; Charani Ranasinghe; Kanta Subbarao; Trent Munro; Paul Young; Keith Chappell. Molecular clamp stabilised Spike protein for protection against SARS-CoV-2. 2020, 1 .

AMA Style

Daniel Watterson, Danushka Wijesundara, Naphak Modhiran, Francesca Mordant, Zheyi Li, Michael Avumegah, Christopher McMillan, Julia Lackenby, Kate Guilfoyle, Geert van Amerongen, Koert Stittelaar, Stacey Cheung, Summa Bibby, Mallory Daleris, Kym Hoger, Marianne Gillard, Eve Radunz, Martina Jones, Karen Hughes, Ben Hughes, Justin Goh, David Edwards, Judith Scoble, Lesley Pearce, Lukasz Kowalczyk, Tram Phan, Mylinh La, Louis Lu, Tam Pham, Qi Zhou, David Brockman, Sherry Morgan, Cora Lau, Mai Tran, Peter Tapley, Fernando Villalon Letelier, James Barnes, Andrew Young, Noushin Jaberolansar, Connor Scott, Ariel Isaacs, Alberto Amarilla, Alexander Khromykh, Patrick Reading, Charani Ranasinghe, Kanta Subbarao, Trent Munro, Paul Young, Keith Chappell. Molecular clamp stabilised Spike protein for protection against SARS-CoV-2. . 2020; ():1.

Chicago/Turabian Style

Daniel Watterson; Danushka Wijesundara; Naphak Modhiran; Francesca Mordant; Zheyi Li; Michael Avumegah; Christopher McMillan; Julia Lackenby; Kate Guilfoyle; Geert van Amerongen; Koert Stittelaar; Stacey Cheung; Summa Bibby; Mallory Daleris; Kym Hoger; Marianne Gillard; Eve Radunz; Martina Jones; Karen Hughes; Ben Hughes; Justin Goh; David Edwards; Judith Scoble; Lesley Pearce; Lukasz Kowalczyk; Tram Phan; Mylinh La; Louis Lu; Tam Pham; Qi Zhou; David Brockman; Sherry Morgan; Cora Lau; Mai Tran; Peter Tapley; Fernando Villalon Letelier; James Barnes; Andrew Young; Noushin Jaberolansar; Connor Scott; Ariel Isaacs; Alberto Amarilla; Alexander Khromykh; Patrick Reading; Charani Ranasinghe; Kanta Subbarao; Trent Munro; Paul Young; Keith Chappell. 2020. "Molecular clamp stabilised Spike protein for protection against SARS-CoV-2." , no. : 1.

Other
Published: 10 September 2020
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The durability of infection-induced SARS-CoV-2 immunity has major implications for public health mitigation and vaccine development. Animal studies1,2 and the scarcity of confirmed re-infection3 suggests immune protection is likely, although the durability of this protection is debated. Lasting immunity following acute viral infection requires maintenance of both serum antibody and antigen-specific memory B and T lymphocytes and is notoriously pathogen specific, ranging from life-long for smallpox or measles4, to highly transient for common cold coronaviruses (CCC)5. Neutralising antibody responses are a likely correlate of protective immunity and exclusively recognise the viral spike (S) protein, predominantly targeting the receptor binding domain (RBD) within the S1 sub-domain6. Multiple reports describe waning of S-specific antibodies in the first 2-3 months following infection7-12. However, extrapolation of early linear trends in decay might be overly pessimistic, with several groups reporting that serum neutralisation is stable over time in a proportion of convalescent subjects8,12-17. While SARS-CoV-2 specific B and T cell responses are readily induced by infection6,13,18-24, the longitudinal dynamics of these key memory populations remains poorly resolved. Here we comprehensively profiled antibody, B and T cell dynamics over time in a cohort recovered from mild-moderate COVID-19. We find that binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection, as expected, with a similar decline in S-specific CD4+ and circulating T follicular helper (cTFH) frequencies. In contrast, S-specific IgG+ memory B cells (MBC) consistently accumulate over time, eventually comprising a significant fraction of circulating MBC. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent subjects to 74 days, with probable additive protection from B and T cells. Overall, our study suggests SARS-CoV-2 immunity after infection is likely to be transiently protective at a population level. SARS-CoV-2 vaccines may require greater immunogenicity and durability than natural infection to drive long-term protection.

ACS Style

Adam K. Wheatley; Jennifer A. Juno; Jing J. Wang; Kevin J. Selva; Arnold Reynaldi; Hyon-Xhi Tan; Wen Shi Lee; Kathleen M. Wragg; Hannah G. Kelly; Robyn Esterbauer; Samantha K. Davis; Helen E. Kent; Francesca L. Mordant; Timothy E. Schlub; David L. Gordon; David S. Khoury; Kanta Subbarao; Deborah Cromer; Tom P. Gordon; Amy W. Chung; Miles P. Davenport; Stephen J. Kent. Evolution of immunity to SARS-CoV-2. 2020, 1 .

AMA Style

Adam K. Wheatley, Jennifer A. Juno, Jing J. Wang, Kevin J. Selva, Arnold Reynaldi, Hyon-Xhi Tan, Wen Shi Lee, Kathleen M. Wragg, Hannah G. Kelly, Robyn Esterbauer, Samantha K. Davis, Helen E. Kent, Francesca L. Mordant, Timothy E. Schlub, David L. Gordon, David S. Khoury, Kanta Subbarao, Deborah Cromer, Tom P. Gordon, Amy W. Chung, Miles P. Davenport, Stephen J. Kent. Evolution of immunity to SARS-CoV-2. . 2020; ():1.

Chicago/Turabian Style

Adam K. Wheatley; Jennifer A. Juno; Jing J. Wang; Kevin J. Selva; Arnold Reynaldi; Hyon-Xhi Tan; Wen Shi Lee; Kathleen M. Wragg; Hannah G. Kelly; Robyn Esterbauer; Samantha K. Davis; Helen E. Kent; Francesca L. Mordant; Timothy E. Schlub; David L. Gordon; David S. Khoury; Kanta Subbarao; Deborah Cromer; Tom P. Gordon; Amy W. Chung; Miles P. Davenport; Stephen J. Kent. 2020. "Evolution of immunity to SARS-CoV-2." , no. : 1.

Mini review
Published: 04 September 2020 in European Journal of Immunology
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The COVID‐19 pandemic caused by the zoonotic coronavirus, SARS‐CoV‐2 has swept the world in 5 months. A proportion of cases develop severe respiratory tract infections progressing to acute respiratory distress syndrome and a diverse set of complications involving different organ systems. Faced with a lack of coronavirus‐specific antiviral drugs and vaccines, hundreds of clinical trials have been undertaken to evaluate repurposed drugs. Convalescent plasma from recovered patients is an attractive option because antibodies can have direct or indirect antiviral activity and immunotherapy works well in principle, in animal models and in anecdotal reports. However, the benefits of convalescent plasma treatment can only be clearly established through carefully designed randomised clinical trials. The experience from investigations of convalescent plasma products for severe influenza offers a cautionary tale. Despite promising pilot studies, large multicentre randomised controlled trials failed to show a benefit of convalescent plasma or hyperimmune intravenous globulin for the treatment of severe influenza A virus infection. These studies provide important lessons that should inform the planning of adequately powered randomised controlled trials to evaluate the promise of convalescent plasma therapy in COVID‐19 patients. This article is protected by copyright. All rights reserved

ACS Style

Kanta Subbarao; Francesca Mordant; Rajeev Rudraraju. Convalescent plasma treatment for COVID‐19: tempering expectations with the influenza experience. European Journal of Immunology 2020, 50, 1 .

AMA Style

Kanta Subbarao, Francesca Mordant, Rajeev Rudraraju. Convalescent plasma treatment for COVID‐19: tempering expectations with the influenza experience. European Journal of Immunology. 2020; 50 (10):1.

Chicago/Turabian Style

Kanta Subbarao; Francesca Mordant; Rajeev Rudraraju. 2020. "Convalescent plasma treatment for COVID‐19: tempering expectations with the influenza experience." European Journal of Immunology 50, no. 10: 1.

Journal article
Published: 02 September 2020 in eLife
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Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

ACS Style

John Huddleston; John R Barnes; Thomas Rowe; Xiyan Xu; Rebecca Kondor; David E Wentworth; Lynne Whittaker; Burcu Ermetal; Rodney Stuart Daniels; John W McCauley; Seiichiro Fujisaki; Kazuya Nakamura; Noriko Kishida; Shinji Watanabe; Hideki Hasegawa; Ian Barr; Kanta Subbarao; Pierre Barrat-Charlaix; Richard A Neher; Trevor Bedford. Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution. eLife 2020, 9, 1 .

AMA Style

John Huddleston, John R Barnes, Thomas Rowe, Xiyan Xu, Rebecca Kondor, David E Wentworth, Lynne Whittaker, Burcu Ermetal, Rodney Stuart Daniels, John W McCauley, Seiichiro Fujisaki, Kazuya Nakamura, Noriko Kishida, Shinji Watanabe, Hideki Hasegawa, Ian Barr, Kanta Subbarao, Pierre Barrat-Charlaix, Richard A Neher, Trevor Bedford. Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution. eLife. 2020; 9 ():1.

Chicago/Turabian Style

John Huddleston; John R Barnes; Thomas Rowe; Xiyan Xu; Rebecca Kondor; David E Wentworth; Lynne Whittaker; Burcu Ermetal; Rodney Stuart Daniels; John W McCauley; Seiichiro Fujisaki; Kazuya Nakamura; Noriko Kishida; Shinji Watanabe; Hideki Hasegawa; Ian Barr; Kanta Subbarao; Pierre Barrat-Charlaix; Richard A Neher; Trevor Bedford. 2020. "Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution." eLife 9, no. : 1.

Preprint content
Published: 02 September 2020
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SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assessed prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD was associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augmented neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines were comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.

ACS Style

Hyon-Xhi Tan; Jennifer A Juno; Wen Shi Lee; Isaac Barber-Axthelm; Hannah G Kelly; Kathleen M Wragg; Robyn Esterbauer; Thakshila Amarasena; Francesca L Mordant; Kanta Subbarao; Stephen J Kent; Adam K Wheatley. Prime-boost protein subunit vaccines against SARS-CoV-2 are highly immunogenic in mice and macaques. 2020, 1 .

AMA Style

Hyon-Xhi Tan, Jennifer A Juno, Wen Shi Lee, Isaac Barber-Axthelm, Hannah G Kelly, Kathleen M Wragg, Robyn Esterbauer, Thakshila Amarasena, Francesca L Mordant, Kanta Subbarao, Stephen J Kent, Adam K Wheatley. Prime-boost protein subunit vaccines against SARS-CoV-2 are highly immunogenic in mice and macaques. . 2020; ():1.

Chicago/Turabian Style

Hyon-Xhi Tan; Jennifer A Juno; Wen Shi Lee; Isaac Barber-Axthelm; Hannah G Kelly; Kathleen M Wragg; Robyn Esterbauer; Thakshila Amarasena; Francesca L Mordant; Kanta Subbarao; Stephen J Kent; Adam K Wheatley. 2020. "Prime-boost protein subunit vaccines against SARS-CoV-2 are highly immunogenic in mice and macaques." , no. : 1.

Preprint content
Published: 28 July 2020
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Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have mild or asymptomatic infection, but the underlying immunological differences remain unclear. We describe clinical features, virology, longitudinal cellular and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who were repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children were similar to their parents at all timepoints. All family members had salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincided with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child had IgG antibody detected against the S1 protein and virus neutralising activity ranging from just detectable to robust titers. Using a systems serology approach, we show that all family members demonstrated higher levels of SARS-CoV-2-specific antibody features than healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological evidence of infection. This raises the possibility that despite chronic exposure, immunity in children prevents establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may therefore not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

ACS Style

Shidan Tosif; Melanie Neeland; Philip Sutton; Paul Licciardi; Sohinee Sarkar; Kevin Selva; Lien Anh Ha Do; Celeste Donato; Zheng Quan Toh; Rachel Higgins; Carolien van de Sandt; Melissa Lemke; Christina Lee; Suzanne Shoffner; Katie Flanagan; Kelly Arnold; Francesca Mordant; Kim Mulholland; Julie Bines; Kate Dohle; Dan Pellicci; Nigel Curtis; Sarah McNab; Andrew Steer; Richard Saffery; Kanta Subbarao; Amy Chung; Katherine Kedzierska; David Burgner; Nigel Crawford. Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19. 2020, 1 .

AMA Style

Shidan Tosif, Melanie Neeland, Philip Sutton, Paul Licciardi, Sohinee Sarkar, Kevin Selva, Lien Anh Ha Do, Celeste Donato, Zheng Quan Toh, Rachel Higgins, Carolien van de Sandt, Melissa Lemke, Christina Lee, Suzanne Shoffner, Katie Flanagan, Kelly Arnold, Francesca Mordant, Kim Mulholland, Julie Bines, Kate Dohle, Dan Pellicci, Nigel Curtis, Sarah McNab, Andrew Steer, Richard Saffery, Kanta Subbarao, Amy Chung, Katherine Kedzierska, David Burgner, Nigel Crawford. Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19. . 2020; ():1.

Chicago/Turabian Style

Shidan Tosif; Melanie Neeland; Philip Sutton; Paul Licciardi; Sohinee Sarkar; Kevin Selva; Lien Anh Ha Do; Celeste Donato; Zheng Quan Toh; Rachel Higgins; Carolien van de Sandt; Melissa Lemke; Christina Lee; Suzanne Shoffner; Katie Flanagan; Kelly Arnold; Francesca Mordant; Kim Mulholland; Julie Bines; Kate Dohle; Dan Pellicci; Nigel Curtis; Sarah McNab; Andrew Steer; Richard Saffery; Kanta Subbarao; Amy Chung; Katherine Kedzierska; David Burgner; Nigel Crawford. 2020. "Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19." , no. : 1.