Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicatedin vitroto similar levels. Booster vaccinations and an rIBV with improvedin vivoreplication may improve the levels of protection.

Gammacoronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease of poultry. Protective immunity is associated with the major structural protein, spike (S) glycoprotein, which induces neutralising antibodies and defines the serotype. Cross-protective immunity between serotypes is limited and can be difficult to predict. In this study, the ability of two recombinant IBV vaccine candidates, BeauR-M41(S) and BeauR-4/91(S), to induce cross-protection against a third serotype, QX, was assessed. Both rIBVs are genetically based on the Beaudette genome with only the S gene derived from either M41 or 4/91, two unrelated serotypes. The use of these rIBVs allowed for the assessment of the potential of M41 and 4/91 S glycoproteins to induce cross-protective immunity against a heterologous QX challenge. The impact of the order of vaccination was also assessed. Homologous primary and secondary vaccination with BeauR-M41(S) or BeauR-4/91(S) resulted in a significant reduction of infectious QX load in the trachea at four days post-challenge, whereas heterologous primary and secondary vaccination with BeauR-M41(S) and BeauR-4/91(S) reduced viral RNA load in the conjunctiva-associated lymphoid tissue (CALT). Both homologous and heterologous vaccination regimes reduced clinical signs and birds recovered more rapidly as compared with an unvaccinated/challenge control group. Despite both rIBV BeauR-M41(S) and BeauR-4/91(S) displaying limited replication in vivo, serum titres in these vaccinated groups were higher as compared with the unvaccinated/challenge control group. This suggests that vaccination with rIBV primed the birds for a boosted humoral response to heterologous QX challenge. Collectively, vaccination with the rIBV elicited limited protection against challenge, with failure to protect against tracheal ciliostasis, clinical manifestations, and viral replication. The use of a less attenuated recombinant vector that replicates throughout the respiratory tract could be required to elicit a stronger and prolonged protective immune response.

Infection of small ruminants with Teladorsagia circumcincta has, until now, been controlled using a combination of pasture management and frequent anthelmintic treatments. Resistance to the commonly used anthelmintics has driven research into the development of a subunit vaccine, encouraged by the demonstration of development of protective immunity in sheep following exposure to this parasite. Local immune effectors in the abomasum, in particular IgA, are thought to play important roles in naturally- and experimentally-acquired immunity. L3s represent the first contact of this pathogen with the host immune system and, herein, the presence of L3 antigen-specific IgA was demonstrated in abomasal mucus from immune sheep. This antibody source was used to immunoaffinity purify and identify IgA-reactive molecules present in L3s. We identified 155 different proteins in this way, including a number of activation-associated secretory proteins, venom allergen-like-type proteins, detoxifying enzymes, galectins and a suite of other potential vaccine candidate molecules. Levels of immunoaffinity-enriched L3 antigen-specific IgA in gastric lymph from previously-infected sheep were statistically significantly higher (P=0.004) than those measured in helminth-free sheep and a statistically significant negative correlation (P=0.005, rs=-0.565) was identified between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and total T. circumcincta burden measured at necropsy. In addition, a statistically significant positive correlation (P=0.007, rs=0.534) was measured between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and the percentage of inhibited L4s enumerated at necropsy. These results indicate that the purified antigens contain components that could be strongly considered as vaccine candidates.

The avian coronavirus, infectious bronchitis virus (IBV), is an economically important infectious disease affecting chickens, with a diverse range of serotypes found globally. The major surface protein, spike (S), has high diversity between serotypes, and amino acid differences in the S1 sub-unit are thought to be responsible for poor cross-protection afforded by vaccination. Here, we attempt to address this, by using epitope mapping technology to identify shared and serotype-specific immunogenic epitopes of the S glycoprotein of three major circulating strains of IBV, M41, QX, and 4/91, via CLIPS peptide arrays based on peptides from the S1 sub-units. The arrays were screened with sera from chickens immunised with recombinant IBV, based on Beau-R backbone expressing heterologous S, generated in two independent vaccination/challenge trials. The screening of sera from rIBV vaccination experiments led to the identification of 52 immunogenic epitopes on the S1 of M41, QX, and 4/91. The epitopes were assigned into six overlapping epitope binding regions. Based on accessibility and location in the hypervariable regions of S, three sequences, ²⁵YVYYYQSAFRPPNGWHLQGGAYAVVNSTN⁵⁴, ⁶⁷TVGVIKDVYNQSVASI⁸², and ⁸³AMTVPPAGMSWSVS⁹⁶, were selected for further investigation, and synthetic peptide mimics were recognised by polyclonal sera. These epitopes may have the potential to contribute towards a broader cross-protective IBV vaccine.

Throughout the global coronavirus pandemic, we have seen an unprecedented volume of COVID-19 researchpublications. This vast body of evidence continues to grow, making it difficult for research users to keep up with the pace of evolving research findings. To enable the synthesis of this evidence for timely use by researchers, policymakers, and other stakeholders, we developed an automated workflow to collect, categorise, and visualise the evidence from primary COVID-19 research studies. We trained a crowd of volunteer reviewers to annotate studies by relevance to COVID-19, study objectives, and methodological approaches. Using these human decisions, we are training machine learning classifiers and applying text-mining tools to continually categorise the findings and evaluate the quality of COVID-19 evidence.