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New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design.

ABSTRACT: Prime/boost vaccination strategies for HIV/SIV vaccine development have been used since the early 1990s and have become an established method for eliciting cell and antibody mediated immunity. Here we focus on induction of protective antibodies, both broadly neutralizing and non-neutralizing, with the viral envelope being the key target antigen. Prime/boost approaches are complicated by the diversity of autologous and heterologous priming vectors, and by various forms of envelope booster immunogens, many still in development as structural studies aim to design stable constructs with exposure of critical epitopes for protective antibody elicitation. This review discusses individual vaccine components, reviews recent prime/boost strategies and their outcomes, and highlights complicating factors arising as greater knowledge concerning induction of adaptive, protective immunity is acquired.

SUBMITTER: Musich T

PROVIDER: S-EPMC6290472 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design.

Musich Thomas T Robert-Guroff Marjorie M

Expert review of vaccines 20160316 8

Prime/boost vaccination strategies for HIV/SIV vaccine development have been used since the early 1990s and have become an established method for eliciting cell and antibody mediated immunity. Here we focus on induction of protective antibodies, both broadly neutralizing and non-neutralizing, with the viral envelope being the key target antigen. Prime/boost approaches are complicated by the diversity of autologous and heterologous priming vectors, and by various forms of envelope booster immunog ...[more]

PMID: 26910195

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Project description:UnlabelledAntivector immunity limits the response to homologous boosting for viral vector vaccines. Here, we describe a new, potent vaccine vector based on replication-competent vesicular stomatitis virus pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus (VSV-GP), which we previously showed to be safe in mice. In mice, VSV and VSV-GP encoding ovalbumin (OVA) as a model antigen (VSV-OVA and VSV-GP-OVA) induced equal levels of OVA-specific humoral and cellular immune responses upon a single immunization. However, boosting with the same vector was possible only for VSV-GP-OVA as neutralizing antibodies to VSV limited the immunogenicity of the VSV-OVA boost. OVA-specific cytotoxic T-lymphocyte (CTL) responses induced by VSV-GP-OVA were at least as potent as those induced by an adenoviral state-of-the-art vaccine vector and completely protected mice in a Listeria monocytogenes challenge model. VSV-GP is so far the only replication-competent vaccine vector that does not lose efficacy upon repeated application.ImportanceAlthough there has been great progress in treatment and prevention of infectious diseases in the past several years, effective vaccines against some of the most serious infections, e.g., AIDS, malaria, hepatitis C, or tuberculosis, are urgently needed. Here, several approaches based on viral vector vaccines are under development. However, for all viral vaccine vectors currently in clinical testing, repeated application is limited by neutralizing antibodies to the vector itself. Here, we have exploited the potential of vesicular stomatitis virus pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus (VSV-GP) as a vaccine platform. VSV-GP is the first replication-competent viral vector vaccine that does not induce vector-specific humoral immunity, i.e., neutralizing antibodies, and therefore can boost immune responses against a foreign antigen by repeated applications. The vector allows introduction of various antigens and therefore can serve as a platform technology for the development of novel vaccines against a broad spectrum of diseases.

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New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design.

Publications

New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design.

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