OA11.03
Background: HIV-1 vaccines ideally induce high magnitude and avidity antibody (Ab) responses to the envelope glycoprotein (Env). In particular, the highly conserved immunodominant region (IDR) of gp41 is an important target for virion capture and ADCC. We compared Ab responses between different regimens and schedules in HIV negative healthy participants (pts) to evaluate the addition of a 3rd MVA dose, spacing between MVA doses, and the inclusion of co-expressed GM-CSF on Ab magnitude and avidity.
Methods: The JS7 (D) and GEO-D03 DNA (Dg) and HIV62 MVA (M) vaccines produce virus-like particles displaying trimeric, membrane-bound Env; the GEO-D03 DNA co-expresses GM-CSF. HVTN 205 enrolled 150 pts in DDMM (0,2,4,6 mo.) and 75 pts in an MM_M (0,2,6 mo.) regimens; HVTN 094 enrolled 15 pt each in DgDgMM_M (0,2,4,6,10 mo) and DgDgM_M (0,2,4,8 mo.) regimens.
Results: All regimens were safe and well tolerated. Two MVA doses generated IgG to IDR gp41 in 73%-100% of participants. The 3rd MVA dose significantly increased the magnitude (HVTN 205) and avidity (HVTN 205 and 094) of this IgG. This response was durable, with 58% of pts still positive 6 months after the 3rd MVA dose in HVTN 205, and the median magnitude among persistent responders declining only ½ log. Increased spacing between the 1st and 2nd MVA inoculations showed significantly enhanced avidity but no difference in magnitude or response rates. Including co-expressed GM-CSF in the DNA prime did not enhance the magnitude or avidity of the Env-specific Ab. At the end of the immunization regimen in HVTN 094, median avidity indices were 34 and 23 for the 3- and 2-dose MVA arms.
Conclusions: The addition of a spaced 3rd MVA boost to a DDMM regimen enhances the magnitude and avidity of the Env-specific Ab response, and appears to be durable 6 months after immunization without additional boosting. ADCC and virion capture assays are being run to evaluate the unique immune profile and promise of this regimen for protection against clade B infection.
