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P19-58 LB. Comparison of the immunogenicity in humans and rhesus macaques of vaccines consisting of DNA priming and MVA boosting and MVA priming and boosting
Retrovirology volume 6, Article number: P422 (2009)
We compare immune responses in humans and rhesus for two popular concepts for an AIDS vaccine, DNA priming and MVA boosting vs MVA priming and boosting.
Identical doses of HIV and SIV Gag-Pol-Env-expressing DNA (3 mg) and MVA (1 × 108 TCID50) vaccines were tested in humans (HVTN 065) (n = 30) and rhesus (Yerkes M11) (n = 8), respectively. Two protocols were used: DNA at weeks 0 and 8, followed by MVA at weeks 16 and 24 (DDMM) or MVA at weeks 0, 8 and 24 (MMM). Assays for T cells (ICS) and anti-Env Ab (ELISA) were conducted at HVTN (human) or Emory Vaccine Center (macaque) labs at one or two weeks post immunizations.
Whereas rhesus had 100% response rates for all parameters, all human response rates were <80%. In both species, DNA priming resulted in both higher and more CD4-biased T cell responses. Humans had higher CD4 than CD8 response rates (77% vs. 42%) and macaques, greater magnitudes of elicited CD4 than CD8 cells (medians of 1.57% vs 0.19%). In both species, DNA-primed CD4 responses had >2.4-fold greater breadth than MVA-primed CD4 cells. Interestingly, both species, for both regimens, had similar peak magnitudes (medians of ~0.15% of total CD8 cells) and breadths of responding CD8 T cells (2 out of 5 tested pools in humans and 5 out of 24 pools in macaques). In both species, MVA-only immunizations elicited the highest anti-Env Ab responses. In humans, MMM elicited more frequent responses (75% vs 27%) and in both species, >2-times higher titer responses than DDMM. Macaques were much more permissive (~50-times) for Ab responses than humans achieving median titers of ~14 μg per ml for the MMM regimen.
(i) DDMM and MMM immunization elicit distinctive patterns of responses and (ii) immune responses in rhesus are only partial predictors for those in humans.
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Robinson, H., Amara, R., Lai, L. et al. P19-58 LB. Comparison of the immunogenicity in humans and rhesus macaques of vaccines consisting of DNA priming and MVA boosting and MVA priming and boosting. Retrovirology 6, P422 (2009) doi:10.1186/1742-4690-6-S3-P422
- Human Response
- Rhesus Macaque
- Great Magnitude
- Similar Peak
- Great Breadth