AIDSWEEKLY Plus, April 29, 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

Separate T- and B-cell immune responses to the HIV envelope antigen may protect against HIV infection.

The findings offer evidence of correlates of immunity to HIV that may point the way to new vaccine strategies.

A third of HIV negative intravenous drug users (IVDUs) tested by an Italian/American research team had antibodies that recognized both HIV and human self antigens.

Moreover, more than three-fourths of these high-risk individuals had helper T cells that produced interleukin 2 (IL-2) in response to HIV envelope peptides.

"[These] responses to the same healthy, seronegative person suggests exposure to the virus without establishment of productive infection," reported researcher Alberto Beretta of S. Raffaele Scientific Institute, Milan, Italy, and colleagues.

"These responses could reflect protective mechanisms that are triggered by the envelope under certain circumstances."

Beretta et al. reported their findings in The Journal of Infectious Diseases ("Human Immunodeficiency Virus Type 1 (HIV-1)-Seronegative Injection Drug Users at Risk for HIV Exposure Have Antibodies to HLA Class I Antigens and T Cells Specific for HIV Envelope," J Inf Dis, 1996:173(2):472-476).

Beretta et al. noted that a previous study showed that macaque monkeys could be protected against challenge infection with simian immunodeficiency virus (SIV) by immunization with a host-cell self antigen: class I histocompatibility leukocyte antigen or HLA (W.L. Chan et al., AIDS 1995;9:223- 8).

The researchers found that the fifth conserved region (C5) of the HIV-1 envelope glycoprotein shares a strong antigenic similarity to human HLA class I antigen.

They therefore searched for HIV/HLA antigens in high-risk HIV seronegative individuals. These studies used a competitive binding assay pitting antibodies from each subject's serum against a monoclonal antibody (MAb M38) specific for two HLA epitopes shared by all HLA-C alleles.

Because cellular immunity is considered the most important anti-HIV immune response, the study cohort was also evaluated for T-helper cells specific for HIV-1 envelope (Env) peptides.

A cohort of 21 IVDUs was identified as HIV negative by ELISA and Western blot assays for HIV antibody, immune- complex-dissociated HIV p24 antigen test, extended viral cultures, and DNA polymerase chain reaction (PCR) analysis.

For the T-helper-cell studies, 75 HIV seronegative subjects at low risk of acquiring HIV infection served as controls. For the HIV/HLA antibody studies, 84 HIV seronegative blood donors and 10 kidney-transplant recipients served as controls.

Despite being negative on standard HIV-1 antibody tests, seven of the 21 IVDUs (33.3 percent) and four of the 94 controls (4.3 percent) had detectable HIV/HLA antibodies.

The researchers detected HIV-1 Env-specific T-helper cell responses in 16 of the 21 IVDUs (76.2 percent) and in two of the 65 controls (3.1 percent).

In an earlier study, Beretta et al. found HIV/HLA antibodies in 59 percent of seronegative sex partners of seropositive individuals but in none of a control group of seronegative couples.

"These data suggest that both HIV/HLA antibodies and Env- T-helper cell responses can be used as markers of exposure to HIV-1 in the absence of signs of detectable HIV-1 infection with other virologic assays or conventional serologic assays," Beretta et al. concluded.

"Further investigation is needed to understand if these responses are important in protection so that they might be exploited for preventive strategies."

The researchers suggested that the finding of HIV/HLA antibodies in the small number of control subjects could be due to exposure to other foreign antigens that share HLA epitopes.

"Undocumented exposure to a retrovirus other than HIV-1 might account for the presence of HIV/HLA antibodies in our controls," Beretta et al. wrote. "Further, given the ubiquity and immunogenicity of microbial glycoproteins, it is plausible that yet other infectious agents induce antibodies with sufficient cross-reactivity to be detectable in our assay."

Collaborating on this study, in addition to the S. Raffaele Scientific Institute researchers, were workers from the National Cancer Institute, Bethesda, Maryland; the University of Medicine and Dentistry of New Jersey, Newark; and Technometrica Inc., Emerson, New Jersey.

The corresponding author for this study is Alberto Beretta, DIBIT, S. Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.