Although mucosal immunity may play a critical role in preventing HIV transmission, it has received very little study. A study of vertical HIV transmission from mother to infant is therefore proposed not only for its own importance but also as a general model for studying the role of mucosal immunity in prevention of HIV transmission. The inclusion in the study of seropositive mothers who have received experimental HIV vaccine also provides an opportunity to assess possible vaccine effects. An important goal os to lay the groundwork for appropriate methodology to evaluate the mucosal effects of future HIV vaccines. The Viral and Rickettsial Disease Laboratory (VRDL) will collaborate with the University of California at San Francisco (UCSF) and with Stanford University in a group effort described in the accompanying Proposal from the core institution (UCSF). The specific roles of the VRDL in this consortium will be (a) isolation of viruses in culture from both mothers and their infected infants, and (b) the characterization of HIV neutralization and related antibody activities in mucosal fluids (and in corresponding serum samples).
Specific aims at the VRDL includes: (1) Isolation of HIV from maternal lymphocytes, plasma and cervico-vaginal fluids and from infant samples; (2) characterization of syncytium-inducing and non-syncytium-inducing isolates; (3) testing for neutralizing secretory IgA and other isotypes of antibody in mucosal secretins, along with antibody characterization by immunofluorescence and Western blot, (4) where neutralization is present, testing for neutralization of autologous isolates and for breadth of neutralization of other isolates; and (5) studying the presence in mucosal fluids of other antibody activities, including antibody-mediated enhancement of HIV, fusion inhibition, reverse transcriptase inhibition and ADCC. All the data will be analyzed in combination with that from the two collaborating laboratories to help elucidate the correlates and mechanisms of protection from vertical transmission, and thus identify mucosal responses which are desirable for induction by future HIV vaccines.
| Goulston, C; McFarland, W; Katzenstein, D (1998) Human immunodeficiency virus type 1 RNA shedding in the female genital tract. J Infect Dis 177:1100-3 |
| D'Souza, M P; Livnat, D; Bradac, J A et al. (1997) Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. AIDS Clinical Trials Group Antibody Selection Working Group. J Infect Dis 175:1056-62 |
| Goulston, C; Stevens, E; Gallo, D et al. (1996) Human immunodeficiency virus in plasma and genital secretions during the menstrual cycle. J Infect Dis 174:858-61 |
