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Abstract
In recent years, heterologous prime-boost vaccines have been demonstrated to be an effective strategy for generating protective immunity, consisting of both humoral and cell-mediated immune responses against a variety of pathogens including HIV-1. Previous reports of preclinical and clinical studies have shown the enhanced immunogenicity of viral vector or DNA vaccination followed by heterologous protein boost, compared to using either prime or boost components alone. With such approaches, the selection of an adjuvant for inclusion in the protein boost component is expected to impact the immunogenicity and safety of a vaccine. In this study, we examined in a mouse model the serum cytokine and chemokine profiles for several candidate adjuvants: QS-21, Al(OH)3, monophosphoryl lipid A (MPLA) and ISCOMATRIX™ adjuvant, in the context of a previously tested pentavalent HIV-1 Env DNA prime-protein boost formulation, DP6-001. Our data revealed that the candidate adjuvants in the context of the DP6-001 formulation are characterized by unique serum cytokine and chemokine profiles. Such information will provide valuable guidance in the selection of an adjuvant for future AIDS vaccine development, with the ultimate goal of enhancing immunogenicity while minimizing reactogenicity associated with the use of an adjuvant. More significantly, results reported here will add to the knowledge on how to include an adjuvant in the context of a heterologous prime-protein boost vaccination strategy in general.
Highlights
The RV144 clinical trial using a viral vector primerecombinant protein boost vaccine demonstrated a low level, but statistically significant protection against HIV-1 infection in Thai volunteers [1,2,3,4]
The RV144 trial employed a canarypox viral vector ALVAC, encoding HIV-1 antigens env, gag, and pol, as a prime, followed by a boost with bi-clade AIDSVAX B/E recombinant gp120 protein boost formulated with adjuvant Al(OH)3
We included cytokines and chemokines associated with activation and chemoattraction of monocytes, macrophages, natural killer cells (NKs) cells, and granulocytes [MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), G-CSF], neutrophils [KC (CXCL1)] and eosinophils [Eotaxin]
Summary
The RV144 clinical trial using a viral vector primerecombinant protein boost vaccine demonstrated a low level, but statistically significant protection against HIV-1 infection in Thai volunteers [1,2,3,4]. The RV144 trial employed a canarypox viral vector ALVAC, encoding HIV-1 antigens env, gag, and pol, as a prime, followed by a boost with bi-clade AIDSVAX B/E recombinant gp120 protein boost formulated with adjuvant Al(OH). A more immunogenic adjuvant than Al(OH) may provide enhanced and long lasting antibody responses, which may improve the level of protection compared to that observed in the RV144 trial. It is very important scientifically to examine how an adjuvant works when it is formulated with Env proteins, and in the context of hosts who have been primed by a gene-based vaccine (such as viral vector or DNA vaccine) encoding antigens similar to the boost
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