Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Concomitant high level T helper and humoral responses in vaccinated rhesus monkeys do not protect against SIV challenge.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 57. Unique Identifier : AIDSLINE PRIM11/94191652 Benveniste O; Vaslin B; Le Grand R; Vogt G; Gras G; Salk J; Dormont D; Laboratoire de Neuropathologie Experimentale et Neurovirologie,; Commissariat a l'Energie Atomique, Fontenay aux Roses, France.
Abstract:
Two groups of 5 rhesus macaques received 3 intramuscular 100 microgram doses of inactivated SIV delta B670 virus, emulsified in adjuvant, at 0, 2, and 7 months. First group (A) received the immunogen in an oil-in-water emulsion consisting of RIBI detox with mycobacterial cell wall skeleton and monophosphoryl lipid A (CWS/MPL). Second group (B) received 2 doses of the immunogen in a water-in-oil emulsion, consisting of incomplete Freund's adjuvant (IFA) containing CWS/MPL (an adjuvant preparation similar to complete Freund's adjuvant), followed by a third dose in IFA alone. A control group (C) of 4 animals remained unvaccinated. All animals were challenged with 10-100 monkey ID50 of SIVmac251 grown in monkey peripheral blood mononuclear cells (PBMC), 3 months after the last dose. Specific humoral response against SIV was assessed using ELISA. Specific activation of T helper cells to SIV was determined by a tritiated thymidine incorporation assay and by determination of the IL2 culture supernatant level using the CTLL IL2 dependent cell line bioassay. As expected, the responses in group B animals were stronger than those in group A. SIV-specific ELISA titers ranged between 10(5)-10(6) in group B and 10(2)-10(4) in group A. Lymphoproliferative responses to the SIV immunogen were observed in all group B animals, but not in any of the group A or C animals. PBMC IL2 production in response to the SIV immunogen was markedly enhanced in the group B, at the day of the infection. IL2 levels ranged between 50 and 500 mUI/ml in group B animals, and were undetectable in groups A and C. Despite the presence of stronger humoral and cellular responses against the challenge virus, none of the group B animals resisted infection. All the monkeys of groups A, B and C were diagnosed as infected on day 14 after challenge. Furthermore, after challenge, all group B animals presented fever and generalized lymphadenopathy. These clinical signs were not observed in groups A and C. Finally, the serum viremia were also higher in the group B animals than in A and C groups. Taken together, these data suggest that the stronger activation of both cellular and humoral immunity does not prevent infection by SIV, and possibly enhance the severity of the clinical symptoms during primo-infection.
Keywords: Animal Antibodies, Viral/BLOOD Antibody Formation Enzyme-Linked Immunosorbent Assay Freund's Adjuvant Immunity, Cellular Lymphocyte Transformation Macaca mulatta Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/*PREVENTION & CONTROL SIV/*IMMUNOLOGY T-Lymphocytes, Helper-Inducer/IMMUNOLOGY Vaccines, Inactivated/*IMMUNOLOGY Viral Vaccines/*IMMUNOLOGY ABSTRACT 940730
M9470866
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
