HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice. NLM AIDSLINE Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice.

AIDS Res Hum Retroviruses. 1998 Sep 20;14(14):1263-9. Unique Identifier : AIDSLINE MED/98435939
Scott DE; Golding H; Huang LY; Inman J; Golding B; Laboratory of Plasma Derivatives, Division of Hematology, Center; for Biologics Evaluation and Research, U.S. Food and Drug; Administration, Bethesda, Maryland 20892, USA.


Abstract: Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4+ T cells. The MHC class II-deficient mouse (II-/-) environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4+ T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses. V3-BA, but not the T-dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3 antibodies, with IgG2b and IgG3 as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-BA in II-/- mice were capable of neutralizing HIV. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients.
Keywords: JOURNAL ARTICLE Animal AIDS Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY Brucella abortus/*IMMUNOLOGY Cytokines/*METABOLISM CD4-Positive T-Lymphocytes/IMMUNOLOGY Disease Models, Animal Heat HIV Antibodies/*BLOOD HIV Envelope Protein gp120/*IMMUNOLOGY HIV-1/*IMMUNOLOGY IgA/BLOOD IgG/BLOOD Immunoglobulin Isotypes Immunologic Deficiency Syndromes/*IMMUNOLOGY Mice Mice, Inbred C57BL Neutralization Tests Peptide Fragments/*IMMUNOLOGY RNA, Messenger/METABOLISM Support, U.S. Gov't, P.H.S. Vaccines, Conjugate/ADMINISTRATION & DOSAGE/*IMMUNOLOGYKWDjournalarticleanimalaidsvaccines/administration&dosage/KWDimmunologybrucellaabortus/KWDimmunologycytokines/KWDmetabolismcd4-positivet-lymphocytes/immunologydiseasemodels,animalheathivantibodies/KWDbloodhivenvelopeproteingp120/KWDimmunologyhiv-1/KWDimmunologyiga/bloodigg/bloodimmunoglobulinisotypesimmunologicdeficiencysyndromes/KWDimmunologymicemice,inbredc57blneutralizationtestspeptidefragments/KWDimmunologyrna,messenger/metabolismsupport,uKWDsKWDgov't,pKWDhKWDsKWDvaccines,conjugate/administration&dosage/KWDimmunology
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Copyright © 1999 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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