17th International AIDS Conference Mexico City, Mexico - August 13 - 18, 2008

ROLE OF NEUTRALIZING ANTIBODIES IN THE BOTTLENECK OF VERTICAL TRANSMISSION

Int Conf AIDS. 2008 Aug 13-18;17 Abstract No. MOAA0303

E. Russell ¹, J. Kwiek², V. Mwapasa³, S. Rogerson⁴, S. Meshnick⁵, R. Swanstrom^6
1University of North Carolina, Microbiology and Immunology, Chapel Hill, United States, ²The Ohio State University, Microbiology, Columbus, United States, ³College of Medicine, Blantyre, Malawi, ⁴University of Melbourne, Victoria, Australia, ⁵University of North Carolina, Epidemiology, Chapel Hill, United States, ⁶University of North Carolina, Center for AIDS Research, Chapel Hill, United States

BACKGROUND: Over one-half million infants are infected with HIV-1 each year either in utero, intrapartum, or through breast milk. There is conflicting evidence for the role maternal neutralizing antibodies may play in preventing or facilitating transmission. A genetic bottleneck has been identified to occur during vertical transmission, but it is unknown which mechanisms select the viral variants that are transmitted to the infant.

METHODS: Using peripheral blood and serum samples from participants of the Malaria and HIV in Pregnancy Study, conducted in Blantyre, Malawi, we analyzed vertical transmission in two ways. First, we tested sera from 103 transmitting (both in utero and intrapartum) and non-transmitting women for neutralizing antibodies against HIV-1 pseudotyped with three different envelopes. Second, we characterized env gene diversity in transmission using single genome amplification of env and sequence analysis of variable region 1 through variable region 5 from five in utero, four intrapartum, and three postpartum mother-infant transmission pairs. These sequences were aligned and analyzed using a phylogenetic tree.

RESULTS: There was no difference in neutralizing antibody titer between mothers who transmitted and those who did not transmit when measured against any of the three envelopes tested. Infant env gene diversity was less than maternal diversity in all 12 pairs tested, with infant sequences clustering to a single branch in the majority of cases.

CONCLUSIONS: Our analysis examined the presence of broadly reactive neutralizing antibodies and whether they could lower the rate of either in utero or intrapartum transmission. We did not find a correlation between vertical transmission and neutralization of the HIV-1 envelopes tested with maternal sera. We confirmed a genetic bottleneck in HIV-1 vertical transmission, and these data extend previous observations to a larger region of the genome, providing more detailed information about the transmitted variants and novel reagents for future studies.

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2008-08-13
MOAA0303

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