Induction of mucosal HIV-specific B and T cell responses after oral immunization with live coxsackievirus B4 recombinants

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• 作者：Rui Gu¹ ; Cristy Stagnar¹ ; Lesya Zaichenko ; Arlene I. Ramsingh ; ^{ramsingh@wadsworth.org}
• 关键词：Coxsackievirus ; Vaccine ; gp41 ; Gag p24 ; Gut mucosa ; Anti-gp41 antibodies ; p24-specific T cell responses
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：21 May, 2012
• 卷：30
• 期：24
• 页码：3666-3674
• 文件大小：1131 K

摘要

Given the limited success of clinical HIV vaccine trials, new vaccine strategies are needed for the HIV pipeline. The present study explored the novel concept that a live enteric virus, with limited disease potential, is a suitable vaccine vector to elicit HIV-specific immune responses in the gut mucosa of immunized mice. Two coxsackievirus B4 (CVB4) vaccine vectors were designed to induce HIV-specific B or T cell responses. A B cell immunogen, CVB4/gp41(2F5), was constructed by expressing an epitope from the membrane proximal external region (MPER) of gp41 as a structural peptide within a surface loop of a capsid protein of CVB4. The T cell immunogen, CVB4/p24(73₃), was constructed previously by expressing a gag p24 sequence as a non-structural peptide at the amino-terminus of the CVB4 polyprotein. The CVB4/gp41(2F5) recombinant was antigenic in mice and elicited anti-gp41 antibodies in both the mucosal and systemic compartments. The route of immunization affected the antibody response since oral delivery of CVB4/gp41(2F5) induced anti-gp41 antibodies in the mucosal but not in the systemic compartment while parenteral delivery induced anti-gp41 antibodies in both compartments. In contrast, oral immunization with CVB4/p24(73₃) elicited both mucosal and systemic gag p24-specific T cell responses. Since coxsackieviruses are ubiquitous in the human population, a key question is whether pre-existing vector immunity will inhibit the ability of a CVB4-based vaccine to induce HIV-specific immune responses. We show that pre-existing vector immunity did not preclude the development of mucosal anti-gp41 antibodies or gag p24-specific T cell responses after oral immunization with the CVB4/HIV recombinants. We suggest that the CVB4/HIV recombinants have the potential to be a viable vaccine product because of ease of delivery, safety, immunogenicity, ease of large-scale production, and storage conditions requiring cold-chain temperatures provided by refrigeration.