Abstract
Development of a successful HIV vaccine is dependent upon a determination of the optimum antigen and adjuvant as well as choosing an optimal site for vaccine delivery. The site of delivery is particularly relevant as HIV transmission generally requires that the virus crosses a mucosal membrane to infect a new host. Here we undertake a pilot study comparing three vaccine delivery routes, two to the oral cavity (intraepithelial (iEp) and needle-free (NF-Injex)) as well as intramuscular (IM) delivery. These vaccinations utilized a recombinant HIV-1 Env trimer 10042.05 from an elite neutralizer, subject VC10042, that has previously induced high titers of cross-clade reactive V1V2 antibodies. The 10042.05.SOSIP fused trimer was administered with adjuvants R848 (Resiquimod), MPLA and Alhydrogel to characterize the innate cellular and anti-HIV Envelope (Env) antibody responses following the administration of the vaccine to the oral mucosa. Oral delivery of the 10042.05.SOSIP induced high titers of anti-V1V2 antibodies, which together with previous studies, indicates an immunogenic bias toward the V1V2 regions in 10042-derived Envs. Both types of oral vaccine delivery resulted in immunologic and serologic responses that were comparable to the IM delivery route. Furthermore, induction of anti-V1-V2 specific antibodies was best following iEp delivery of the oral vaccine identifying this as the optimal method to orally deliver this vaccine formulation.
Highlights
The HIV-1 epidemic continues to exact a massive human and economic toll
Our findings indicate that the iEp oral delivery route was superior to the needle-free approach with regard to the extent of the anti-V1-V2 antibody induction and that oral vaccination of Env trimers is a viable route for inducing immunity against HIV-1
We utilized a native-like trimer derived from an elite neutralizer, 10042.05.SOSIP, to evaluate the induction of anti-HIV Env antibody responses following different oral mucosal vaccination of Rhesus macaques
Summary
The HIV-1 epidemic continues to exact a massive human and economic toll. Efforts to increase access to antiretroviral therapies have brought the number of yearly deaths from HIV-1 to below 1 million per year (UNAIDS). Fc-mediated functional activity of the anti-V1V2 antibodies are associated with reduced risk of infection [3,4,5,6,7,8,9] These findings imply that non-neutralizing activities can contribute to protection in an eventual vaccine. There are currently licensed mucosally-administered vaccines for five different pathogens, most of which are administered orally to the gastro-intestinal associated lymphoid tissue (e.g., poliovirus) or nasally (e.g., influenza) [19, 20] Such vaccines are known to elicit both local and systemic immune responses but can show variable efficacy, and some carry safety concerns due to their formulation. Our findings indicate that the iEp oral delivery route was superior to the needle-free approach with regard to the extent of the anti-V1-V2 antibody induction and that oral vaccination of Env trimers is a viable route for inducing immunity against HIV-1
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