Defining the correlates of protection necessary to manage the COVID-19 pandemic requires the analysis of both antibody and T cell parameters, but the complexity of traditional tests limits virus-specific T cell measurements. We tested the sensitivity and performance of a simple and rapid SARS-CoV-2 spike protein–specific T cell test based on the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2-vaccinated individuals (n = 112), convalescent asymptomatic and symptomatic COVID-19 patients (n = 130), and SARS-CoV-1–convalescent individuals (n = 12). The sensitivity of this rapid test is comparable to that of traditional methods of T cell analysis (ELISPOT, activation-induced marker). Using this test, we observed a similar mean magnitude of T cell responses between the vaccinees and SARS-CoV-2 convalescents 3 months after vaccination or virus priming. However, a wide heterogeneity of the magnitude of spike-specific T cell responses characterized the individual responses, irrespective of the time of analysis. The magnitude of these spike-specific T cell responses cannot be predicted from the neutralizing antibody levels. Hence, both humoral and cellular spike–specific immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.

The pandemic spread of a novel coronavirus - SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress. Global economies are also spiraling towards a recession in fear of this new life-threatening disease. Vaccines that prevent SARS-CoV-2 infection and therapeutics that reduces the risk of severe Covid-19 are thus urgently needed. A rapid method to derive antiviral treatment for Covid-19 is the use of convalescent plasma derived hyperimmune globulin. However, both hyperimmune globulin and vaccine development face a common hurdle - the risk of antibody-mediated disease enhancement. The goal of this review is to examine the body of evidence supporting the hypothesis of immune enhancement that could be pertinent to Covid-19. We also discuss how this risk could be mitigated so that both hyperimmune globulin and vaccines could be rapidly translated to overcome the current global health crisis.

Asia remains vulnerable to new and emerging infectious diseases. Understanding how to improve next generation sequencing (NGS) use in pathogen surveillance is an urgent priority for regional health security. Here we developed a pathogen genomic surveillance assessment framework to assess capacity in low-resource settings in South and Southeast Asia. Data collected between June 2022 and March 2023 from 42 institutions in 13 countries showed pathogen genomics capacity exists, but use is limited and under-resourced. All countries had NGS capacity and seven countries had strategic plans integrating pathogen genomics into wider surveillance efforts. Several pathogens were prioritized for human surveillance, but NGS application to environmental and human–animal interface surveillance was limited. Barriers to NGS implementation include reliance on external funding, supply chain challenges, trained personnel shortages and limited quality assurance mechanisms. Coordinated efforts are required to support national planning, address capacity gaps, enhance quality assurance and facilitate data sharing for decision making.

Protection offered by coronavirus disease 2019 (COVID-19) vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking. We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals (n = 55) who were either primed with Ad26.COV2.S only (n = 13) or were boosted with a homologous (Ad26.COV2.S, n = 28) or heterologous (BNT162b2, n = 14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n = 16) or double (n = 44) dose of BNT162b2. We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals. In contrast, the impact of the homologous boost was quantitatively minimal in Ad26.COV2.S-vaccinated individuals, and Spike-specific antibodies and T cells were narrowly focused to the S1 region. Despite the small sample size of the study and the lack of well-defined correlates of protection against COVID-19, the immunological features detected support the utilization of a heterologous vaccine boost in individuals who received Ad26.COV2.S vaccination. This study is partially supported by the Singapore Ministry of Health’s National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001, and COVID19RF-008), The Medical College St. Bartholomew’s Hospital Trustees – Pump Priming Fund for SMD COVID-19 Research.

Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a high throughput serological technology that is revolutionizing the manner in which we track antibody profiles. In this review, we mainly focus on its application to viral infectious diseases. Through the pull-down of patient antibodies using peptide-tile-expressing T7 bacteriophages and detection using next-generation sequencing (NGS), PhIP-Seq allows the determination of antibody repertoires against peptide targets from hundreds of proteins and pathogens. It differs from conventional serological techniques in that PhIP-Seq does not require protein expression and purification. It also allows for the testing of many samples against the whole virome. PhIP-Seq has been successfully applied in many infectious disease investigations concerning seroprevalence, risk factors, time trends, etiology of disease, vaccinology, and emerging pathogens. Despite the inherent limitations of this technology, we foresee the future expansion of PhIP-Seq in both investigative studies and tracking of current, emerging, and novel viruses. Following the review of PhIP-Seq technology, its limitations, and applications, we recommend that PhIP-Seq be integrated into national surveillance programs and be used in conjunction with molecular techniques to support both One Health and pandemic preparedness efforts.

A self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR ^® -COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8 ⁺ T lymphocyte response. Assaying for intracellular cytokine staining for IFN-γ and IL-4 positive CD4 ⁺ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.