Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein r Ov -ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the r Ov -ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of r Ov -ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established r Ov -ASP-1’s adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of r Ov -ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-r Ov -ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus r Ov -ASP-1 and showed that r Ov -ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the r Ov -ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.
【초록키워드】 Efficacy, Vaccine, vaccination, antibody, IL-6, Antibody Response, Th1, Influenza virus, host response, Protein, mice, RBD, NHPs, sera, Effectiveness, antigens, adjuvant, Th2 response, utility, non-human primate, IFN-γ, Protective, TNF-α, IL-2, administration, anti-RBD, DC, bystander, Activation, maturation, protective immune response, IgG2a, naïve, Th1 cytokines, titre, SARS-CoV spike protein, first vaccination, vaccine antigen, element, primate, virus strains, immunized, Onchocerca volvulus, adjuvanticity, Course, different, was used, reported, subsequent, provided, functional, promote, the receptor-binding domain, induce, not affect, upregulated, retained, promoted,