7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:40 (abstract no. M.A.74)
Ugen KE, Goedert J, Kieber-Emmons T, Merva M, Boyer J, Williams WV, Weiner DB; The Wistar Institute, Department of Medicine, University of Pennsylvania, Philadelphia, PA

OBJECTIVE: Understanding the contribution of the humoral immune response to the functions of the HIV envelope in HIV mediated viral entry processes. Anti-syncytial and group specific neutralization activity are observed most frequently in the asymptomatic patient population. High immune responses to the V3 loop region or other regions as defined with synthetic peptides and the ability of several specific peptides corresponding to defined regions of gp120 and 41, including the V3 loop region, to induce protective in vitro immune responses in experimental animals in general supports this contention. A correlation exists between specific humoral immune responses in HIV infected pregnant women and a lack of transmission of HIV infection to the fetus. STUDIES: We have continued to examine the entry related functions of the HIV-1 (HXB2 isolate) envelope using a library of 110 envelope derived synthetic peptides screened against two selected groups of patients 1) adult patients with high neutralizing and antisyncytial activity, and 2) a maternal sera panel divided into mothers who do and do not transmit HIV infection to their fetuses. Based on our mapping studies we raised peptide based antisera to regions of the HIV-1 viral envelope which we have observed reactivity to in these protective patient seras. A subset of our antisera outside the neutralizing loop appears to disrupt entry events of HIV-1 and may have protective value in immunization strategies. One epitope in particular maps to the carboxy region of gp120 and clearly elicits very significant neutralizing activity. Data will be presented describing 14 other now clearly defined areas which do not contain similar activity. We will also present data on a large number of other peptide defined regions. Importantly we have reconstructed the group specific protective activity of patient sera through defined combinations of anti-peptide sera.

CONCLUSIONS: Our site specific serology studies will help in the design of immunological reagents which block HIV entry and offer broadly protective anti-HIV immune responses.

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