- Oral presentation
- Open Access
Phase 2a safety and immunogenicity testing of DNA and recombinant modified vaccinia ankara virus vaccines expressing virus-like particles
© Goepfert et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Modify Vaccinia Ankara Virus
- Avidity Index
- Antibody Avidity
- Immunogenicity Testing
The Phase 2a HVTN 205 trial was undertaken to further compare full-dose regimens of DNA priming with MVA boosting and MVA priming and boosting.
150 vaccinia-naïve participants were inoculated i.m. via needle and syringe with 3 mg of pGA2/JS7 DNA at months 0 and 2, and 1x108 TCID50 of MVA/HIV62B at months 4 and 6 (DDMM regimen). 75 participants received 1x108 TCID50 of MVA/HIV62B at months 0, 2, and 6 (MMM regimen) and 75 received placebo. While the safety data are still blinded, the vaccine regimens appeared safe and well tolerated. Immune studies were performed at 2 weeks following the final vaccination.
Similar to Phase 1 testing, the DDMM regimen induced higher rates of T cell responses whereas the MMM regimen induced higher rates of antibody responses. CD4 T cell responses were elicited in 65% of the DDMM and 43% of the MMM recipients (p=0.01) whereas CD8 T cells were induced in 22% and 16%, respectively. The majority of T cells were directed against Gag with fewer against Env and only occasional responses to Pol. gp120 IgG antibodies were demonstrated in 45% and 68% of the DDMM and MMM recipients, respectively (p=0.001). gp41 IgG antibodies were seen in over 90% of both groups. The magnitudes of serum IgG responses exceeded the magnitudes of serum IgA responses by >10 fold with higher IgG to IgA responses being present in the MMM group (p=0.03). The antibody avidity index to the gp41 immunodominant epitope, a preclinical correlate of protection against infection demonstrated levels of affinity maturation comparable to preclinical studies. Sporadic weak neutralizing activity against Tier 1 and Tier 2 viruses was seen in both groups and was greater for MVA alone.
The vaccine safety data and immune responses seen here are supportive of further testing.
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.