IMMUNOGENICITY OF A RECOMBINANT MEASLES-HIV-1 CLADE B CANDIDATE VACCINE

Monday, 8th of September 2014 Print
[source]PLoS One[|source]

The characteristics of a live attenuated measles vaccine (MV) make it an attractive candidate vaccine vector. In turn, a reverse genetics system for MV has been established, allowing the production of recombinant MV with additional foreign genetic material. Various vectors based on measles vaccine strains have been developed to stably express a variety of genes, or combinations of genes, of large size over more than twelve passages. These vectors have been shown to induce long-lasting humoral and cellular immune responses to the transgenes, even in presence of pre-existing immunity to MV

In this report, the authors generated a recombinant measles vector expressing the F4 antigen, a fusion protein consisting of HIV-1 Clade B p17, p24, RT and Nef antigens. The immunogenicity of the resulting MV1-F4 candidate vaccine was investigated in mice and cynomolgus macaques. The results presented here show that MV1-F4 vaccination induced both cellular and humoral immune responses against the HIV-1 F4 insert, which were boostable resulting in increased immunogenicity. More details on the endpoints measured and recommendations are accessible at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511521/

 

ABSTRACT

Live attenuated measles virus is one of the most efficient and safest vaccines available, making it an attractive candidate vector for a HIV/AIDS vaccine aimed at eliciting cell-mediated immune responses (CMI). Here we have characterized the potency of CMI responses generated in mice and non-human primates after intramuscular immunization with a candidate recombinant measles vaccine carrying an HIV-1 insert encoding Clade B Gag, RT and Nef (MV1-F4). Eight Mauritian derived, MHC-typed cynomolgus macaques were immunized with 105TCID50 of MV1-F4, four of which were boosted 28 days later with the same vaccine. F4 and measles virus (MV)-specific cytokine producing T cell responses were detected in 6 and 7 out of 8 vaccinees, respectively. Vaccinees with either M6 or recombinant MHC haplotypes demonstrated the strongest cytokine responses to F4 peptides. Polyfunctional analysis revealed a pattern of TNFα and IL-2 responses by CD4+ T cells and TNFα and IFNγ responses by CD8+ T cells to F4 peptides. HIV-specific CD4+ and CD8+ T cells expressing cytokines waned in peripheral blood lymphocytes by day 84, but CD8+ T cell responses to F4 peptides could still be detected in lymphoid tissues more than 3 months after vaccination. Anti-F4 and anti-MV antibody responses were detected in 6 and 8 out of 8 vaccinees, respectively. Titres of anti-F4 and MV antibodies were boosted in vaccinees that received a second immunization. MV1-F4 carrying HIV-1 Clade B inserts induces robust boostable immunity in non-human primates. These results support further exploration of the MV1-F4 vector modality in vaccination strategies that may limit HIV-1 infectivity.

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