Immunization with HIV-1 SF162-derived Envelope gp140 proteins does not protect macaques from heterologous simian-human immunodeficiency virus SHIV89.6P infection

• Published in: Virology (New York, N.Y.) N.Y.), 2006-06, Vol.349 (2), p.276-289
• Main Authors: Xu, Rong, Srivastava, Indresh K., Kuller, LaRene, Zarkikh, Irina, Kraft, Zane, Fagrouch, Zahra, Letvin, Norman L., Heeney, Jonathan L., Barnett, Susan W., Stamatatos, Leonidas
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Animals; CD4 Lymphocyte Count; Disease Models, Animal; env Gene Products, Human Immunodeficiency Virus; Enzyme-Linked Immunosorbent Assay; Gene Products, env - genetics; Gene Products, env - immunology; HIV Antibodies - blood; HIV Env gp140; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - immunology; HIV-1 - physiology; HIV-1SF162; Human immunodeficiency virus 1; Interferon-gamma - biosynthesis; Leukocytes, Mononuclear - immunology; Macaca; Macaca mulatta; Neutralization Tests; Neutralizing antibodies; RNA, Viral - blood; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - immunology; SHIV89.6P; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - immunology; Simian/human immunodeficiency virus; T cell responses; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Viral Load
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.01.043

Immunization by the SF162gp140 or the ΔV2gp140 HIV-1 envelope proteins results in the generation of strong homologous neutralizing antibodies (NAbs) that offer similar degree of protection from disease-development to macaques challenged with homologous virus. These two immunogens elicit weak cross-reactive NAbs and their effectiveness against heterologous challenge is currently unknown. To examine this issue, we immunized macaques with SIVGag p55 and either the SF162gp140 or the ΔV2gp140 and challenged them intravenously with SHIV-89.6P. All animals became infected but previous immunization with SF162gp140 accelerated the development of anti-SHIV89.6P neutralizing antibody responses following infection. ΔV2gp140 is derived from SF162gp140 following the deletion of 30 amino acids and one N-linked glycosylation site from the V2 loop. Our results suggest that even small differences in HIV Envelope immunogen structure can affect the neutralizing antibody responses generated following infection.