Abstract
Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-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 rOv-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 rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-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 rOv-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-rOv-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 rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-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.
Highlights
The use of an adjuvant is a key element in promoting vaccine effectiveness because it can stimulate the immune system and accelerate, prolong, or enhance antigen-specific immune responses, even when used in combination with weak vaccine antigens [1]
We previously reported that rOv-ASP-1 could effectively induce a mixed, but Th1-skewed immune response against rS and rRBD in immunized mice [27]
The rOv-ASP-1 adjuvant enhances immune responses in a sequential influenza vaccine Using a mouse model in which we first immunized mice with rRBD of SARS-CoV, we evaluated the efficacy of rOv-ASP-1 adjuvanticity in a sequential vaccination in which we used the HAs of three influenza viruses (A/Brisbane/59/2007, IVR-148 (H1N1); A/Uruguay/716/2007, NYMC X-175C (H3N2); and B/Brishbane/60/2008) as the model antigens
Summary
The use of an adjuvant is a key element in promoting vaccine effectiveness because it can stimulate the immune system and accelerate, prolong, or enhance antigen-specific immune responses, even when used in combination with weak vaccine antigens [1]. In the U.S, Alum remains the sole FDA-approved adjuvant for general use of vaccines [2]. Adjuvants are important in guiding the type of adaptive response that is induced after vaccination and that is most effective against incoming infections. The development of novel adjuvants that stimulate discrete subsets of immune cells, in particular, cytotoxic T-lymphocytes (CTL), is required to unleash the full potential of new vaccines and immunotherapy strategies [5]. Interest in developing new adjuvants has increased significantly over the past decade, as highlighted by the following issues [6,7]: 1) the inability of traditional approaches to develop successful vaccines against ‘‘difficult’’ organisms such as HIV and HCV; 2) the emergence of epidemics or outbreaks of new infectious diseases with high mortality, especially those causing serious threats to public health and socioeconomic stability worldwide (e.g., SARS, Ebola, West Nile, Dengue, pandemic flu and nvCJD); 3) the re-emergence of ‘‘old’’ infections like tuberculosis; 4) the continuing spread of antibiotic-resistant bacteria; and 5) the increased threat of bioterrorism. The molecular design of potently adjuvanted vaccines that would enhance antigen uptake in vivo and potentially simplify their adjuvant requirements would be highly desirable [8]
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