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Highly pathogenic avian influenza viruses (HPAIV) have been responsible for causing several severe outbreaks across the world. To protect poultry farms and to prevent the possible spread of new influenza pandemics, vaccines that are both efficacious and low-cost are in high demand. We produced stable, large hemagglutinin H5 oligomers in planta by the specific interaction between S•Tag and S•Protein. H5 oligomers combined via S•Tag::S•Protein interaction in plant crude extracts induced strong humoral immune responses, strong neutralizing antibody responses, and resistance in chickens after challenge with a wild type HPAIV H5 virus strain. In all three parameters, plant crude extracts with H5 oligomers induced better responses than crude extracts containing trimers. The neutralizing antibodies induced by by two-dose and one dose immunization with an adjuvanted crude extract containing H5 oligomer protected vaccinated chickens from two lethal H5N1 virus strains with the efficiency of 92% and 100%, respectively. Following housing vaccinated chickens together with ten non-immunized chickens, only one of these chickens had detectable levels of the H5N1 virus. To facilitate the easy storage of a candidate vaccine, the H5 oligomer crude extracts were mixed with adjuvants and stored for 3.5 and 5.5 months at 4 °C, and chickens were immunized with these crude extracts. All these vaccinated chickens survived after a lethal H5N1 virus challenge. H5 oligomer crude extracts are comparable to commercial vaccines as they also induce strong virus-neutralizing immune responses following the administration of a single dose. The cost-effective production of plant crude extract vaccine candidates and the high stability after long-term storage will enable and encourage the further exploration of this technology for veterinary vaccine development.

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Vaccines are very effective in providing protection against many infectious diseases. However, it has proven difficult to develop highly efficacious vaccines against some pathogens and so there is a continuing need to improve vaccine technologies. The first successful and widely used vaccines were based on attenuated pathogens (e.g., laboratory passaged Pasteurella multocida to vaccinate against fowl cholera) or closely related non-pathogenic organisms (e.g., cowpox to vaccinate against smallpox). Subsequently, live vaccines, either attenuated pathogens or non-pathogenic microorganisms modified to deliver heterologous antigens, have been successfully used to induce protective immune responses against many pathogens. Unlike conventional killed and subunit vaccines, live vaccines can deliver antigens to mucosal surfaces in a similar manner and context as the natural infection and hence can often produce a more appropriate and protective immune response. Despite these advantages, there is still a need to improve the immunogenicity of some live vaccines. The efficacy of injectable killed and subunit vaccines is usually enhanced using adjuvants such mineral salts, oils, and saponin, but such adjuvants cannot be used with live vaccines. Instead, live vaccines can be engineered to produce immunomodulatory molecules that can stimulate the immune system to induce more robust and long-lasting adaptive immune responses. This review focuses on research that has been undertaken to engineer live vaccines to produce immunomodulatory molecules that act as adjuvants to increase immunogenicity. Adjuvant strategies with varying mechanisms of action (inflammatory, antibody-mediated, cell-mediated) and delivery modes (oral, intramuscular, intranasal) have been investigated, with varying degrees of success. The goal of such research is to define adjuvant strategies that can be adapted to enhance live vaccine efficacy by triggering strong innate and adaptive immune responses and produce vaccines against a wider range of pathogens.

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In the midst of the Covid-19 pandemic, ethicists, researchers, and journalists have recommended studies that deliberately infect healthy volunteers with the coronavirus as a scientific means of expediting vaccine development. In this essay, we trace the history of infection challenge experiments and reflect on the Nuremberg Code of 1947, issued in response to brutal human experiments conducted by Nazi investigators in concentration camps. We argue that the Code continues to offer valuable guidance for assessing the ethics of this controversial form of research, with respect particularly to the acceptable limits to research risks and the social value of research necessary to justify exposing human participants to these risks.

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This manuscript explores the ethics of human inoculation experiments in young healthy adults with wild-type severe acute respiratory sydrome coronavirus 2 (SARS-CoV-2) as a tool to evaluate vaccine efficacy in the context of the Nuremberg Code, the Declaration of Helsinki, and the Belmont Report, and in the context of dose-response relationships with infectious agents. Despite societal pressure to develop a SARS-CoV-2 challenge model to evaluate vaccines, we argue that there are substantial risks that cannot be adequately defined because the dose of SARS-CoV-2 that causes severe disease in young adults is unknown. In the absence of curative therapy, even if a volunteer consents, longstanding ethical codes governing human subjects research preclude the conduct of such experiments.

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Feline calicivirus (FCV) is a virus that causes respiratory disease in cats. In this study, the FCV TIG-1 was isolated from Siberian tiger feces collected in 2014 in Heilongjiang Province, China. Phylogenetic analysis among TIG-1 and other FCVs showed that TIG-1 does not share the same lineage with other FCV isolates from Heilongjiang or other regions in China but is located in the same cluster with the FCV strain Urbana, which was isolated from the United States. The growth kinetics in vitro and the pathogenicity in cats between TIG-1 and the domestic cat-origin FCV strain F9 (vaccine strain) and strain 2280 were compared. We found that the growth kinetics of strains TIG-1 and 2280 were faster than that of strain F9 from 12h to 36h post-infection, indicating that strains TIG-1 and 2280 produce infectious virions and reach peak yields earlier. Challenge experiments in cats showed that TIG-1 grew faster than the other two strains in the lungs of cats and that TIG-1 is a virulent FCV with 100% morbidity and lethality. In addition, the histopathological results showed that the virulent TIG-1 strain directly led to severe lung tissue damage and indirectly led to intestinal damage. The results presented here show that a tiger-origin FCV exhibits high virulence in cats.

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