Volume 9 Supplement 2
Immunogenicity of a universal HIV-1 vaccine vectored by DNA, MVA and CHADV-63 in a Phase I/IIA clinical trial
© Borthwick et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
The major challenge facing both antibody and T cell-eliciting vaccines against HIV-1 is the extreme variability of the HIV-1 genome: a successful vaccine has to effectively target diverse HIV-1 strains circulating in the population and then must deal with ongoing virus escape in infected individuals. To address these issues, we assembled a vaccine immunogen HIVconsv from the functionally most conserved regions (not epitopes) of the HIV-1 proteome.
A gene coding for the HIVconsv immunogen was inserted into plasmid DNA (D), modified vaccinia virus Ankara (MVA; M) and non-replicating adenovirus of a chimpanzee origin ChAdV-63 (C). Currently, combined heterologous prime-boost regimens of these vaccines, namely CM, DDDCM and DDDMC, are being evaluated in a phase I/IIa trial HIV-CORE002 in healthy HIV-1/2-negative volunteers in Oxford.
Preliminary data indicate that the vaccines are well tolerated and show high immunogenicity. Following the CM regimen, vaccine-induced T cell frequencies reached a median of 5150 (range 1475 to 16495) SFU/106 PMBC ex vivo one week post MVA vaccination. DNA priming increased subsequent T cell responses to ChAdV-63 vaccination (median: C 577 and DDDC 1328 SFU/106 PBMC) and ELISpot responses again peaked 1 week following MVA (median 4500; range 2260-7960 SFU/106 PBMC). Matrix analyses of the participants following CM vaccination showed that T cells responded to a range of peptides across the length of HIVconsv. The CM regimen elicited IFN-γ in both CD4+ and CD8+ T cell subsets and polyfunctional (IFN-γ & TNF-α) responses to HIVconsv peptides.
Presented data will be very much work in progress. Nevetheless, the HIVconsv vaccines have so far induced T cell responses superior to other HIV-1 vaccine candidates tested to date. ChAdV-63 is the first adenovirus of chimp origin delivering an HIV-1-derived immunogen that has reached the clinic.
The work is supported by Medical Research Council UK.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.