Evaluation of a natural challenge model of zebrafish with Influenza A virus

Influenza A virus (IAV) presents as a global public health concern, resulting in an extensive burden on morbidity and mortality rates in humans. IAV has high mutation rates, influencing emergence of new virus strains, which could lead to increased antiviral resistivity and altered virulence. Although prevention and treatment of influenza infections have been improved, animal models still play a major role in understanding of host responses and the pathogenesis of IAV infection. Zebrafish are useful host models for evaluating infectious diseases processes, especially with the ability to manipulate the genome of zebrafish. Research by others have shown that parenteral applied IAV could infect zebrafish embryos, supporting that zebrafish could be used as a host model of IAV infection. In this study, our goal was to determine if viral host adaptation or mucosal perturbation will provide a more useful model by allowing routes of infection through the respiratory epithelium. The prototype strain A/Puerto Rico/8/1934(H1N1) (abbreviated as APR8) was selected and used in this study. To host adapt the virus we attempted to propagate APR8 in SJD and ZF zebrafish cell lines, and to infect zebrafish embryos at 24-48 hours post-fertilization. In the process, we found that the zebrafish embryos and cell lines were highly sensitive to the antibiotics and trypsin used in the medium to propagate the virus. We have therefore modified virus propagation procedures to optimize cell line production and embryo challenges. As a future study, once the adaption is successful, we will do comparative challenges of zebrafish embryos with parent strain and adapted virus, with and without mucosal perturbation. If successful, the zebrafish adapted virus can be used in pathogenesis, and innate defense research and comparative research will reveal the critical requirement for IAV adapting to a distant host

Correlates of protection against SARS-CoV-2 in rhesus macaques

Recent studies have reported the protective efficacy of both natural1 and vaccine-induced2–7 immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques (Macaca mulatta) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8+ T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents.Bill & Melinda Gates Foundation (Grant INV-006131)National Institutes of Health (Grants OD024917, AI129797, AI124377, AI128751, AI126603 and CA260476

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials