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  • br Differences among flavivirus vaccines and implications

    2022-08-11


    Differences among flavivirus vaccines and implications for CD4 T cell immunity There are currently three classes of flavivirus vaccines in use – live-attenuated virus (for immunoprophylaxis against YF and JE), whole inactivated virus vaccines (JE, TBE) and chimeric vaccines (JE, DEN). The chimeric viruses were constructed by replacing the genes for the viral membrane (prM-E) proteins from the live-attenuated YF-17D vaccine strain with those of heterologous flaviviruses (Chimerivax™ technology) (Fig. 1d). The first licensed DEN vaccine (Dengvaxia®) contains four chimeric live viruses with prM and E of each of the four DEN serotypes [79]. In addition, there is a large number of different flavivirus vaccine candidates in preclinical and clinical development. These include inactivated vaccines, virus-like particles, live-attenuated vaccines, chimeric vaccines, recombinant E protein subunit vaccines, viral vector vaccines and nucleic acid-based vaccines (reviewed in [10,80,81]. Because of the principal differences between these vaccines, there will likely be differences in the effector mechanisms that correlate with protective immunity. For instance, inactivated vaccines induce CD4 T helper cell types and multicytokine producing tbtu that are different from those elicited by natural infection or live-attenuated virus vaccines [47,82]. The mechanisms underlying these distinct response patterns may reflect possible effects of antigen abundance and innate immune signals related to viral replication, but could also be explained by antigen modifications in the vaccine preparation, formalin treatment, addition of adjuvants and the route of immunization [83,84]. In addition, certain epitope responses may be established only in the course of infection, but not in individuals who receive inactivated vaccines. Evidence from a comparison of CD4 T cell specificities in TBE virus infected and vaccinated individuals has indicated that certain epitope regions become accessible for processing only after virus infection, but not after vaccination with inactivated vaccines, in which the E protein is fixed by treatment with formalin [25]. Finally, whether or not a viral protein is available in a vaccine will obviously influence the response. It has been speculated that the suboptimal efficacy of the chimeric DEN vaccine may in part be due to the lack of a protective T cell response, since the capsid and NS proteins are derived from YF virus [10]. As only very few epitopes from each protein are selected in an individual response, vaccines lacking the entire capsid protein presumably yield quite small numbers of epitopes for cognate T-/B cell interactions to support antibody and memory formation. Thus, whether sufficient T cell help to protective and durable antibodies can be generated by these vaccines or whether the lack of epitopes derived from NS proteins plays a role, needs to be further investigated. Considering the critical importance of CD4 T cells in protective immunity, it would be desirable to augment CD4 T cell responses for improving vaccine efficacy. This may be achieved by generating broadly flavivirus cross-reactive CD4 T cell responses through sequential immunizations for flaviviruses sharing CD4 T cell epitopes, as has been recently shown in mice [36]. Furthermore, novel adjuvants targeting innate immune receptors have been discovered that are especially powerful to enhance important CD4 T cell subsets, such as Tfh cells that are involved in high-affinity antibody production, and thus provide new opportunities to improve vaccine responses [85,86]. Further expanding on these findings will significantly advance our understanding of the mechanisms regulating important T cell functions, which is a key step toward the development of effective novel vaccines.
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    Introduction The reproductive performance of sows is an important economic trait. Given that the health status of sows can affect its fertility, pig producers vaccinate their pigs to improve their resistance to multifarious diseases. However, some vaccines do not work well, and inappropriate vaccination may even cause infections on the entire pig group (Hu and Zhang, 2014; Seo et al., 2014; Nan et al., 2017). The immunity of pregnant sows affects not only their own health condition but also the survival rate of piglets (Dvorak et al., 2018), thereby affecting the profitability of pig producers. Discovering effective immunity molecular markers for gestating sows and using them for molecular breeding in sow selection will provide a great opportunity to improve the disease resistance of sows, increase the number of healthy piglets, and improve sow longevity.