Inhibition of HIV‐1 entry by antibodies: potential viral and cellular targets

• Published in: Journal of internal medicine Vol. 262; no. 1; pp. 26 - 43
• Main Authors: Phogat, S., Wyatt, R. T., Karlsson Hedestam, G. B.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2007; Blackwell Science
• Subjects: AIDS Vaccines - immunology; Biological and medical sciences; envelope glycoprotein; Epitopes - immunology; Gene Products, env - immunology; General aspects; HIV Antibodies - immunology; HIV Infections - immunology; HIV-1 - immunology; HIV‐1; Human immunodeficiency virus 1; Human viral diseases; Humans; incorporated proteins; Infectious diseases; Medical sciences; Medicin och hälsovetenskap; neutralizing antibodies; receptors; Receptors, HIV - immunology; vaccine; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Proteins - immunology; Virus Internalization; HIV-1; Targeting; HIV-1 virus; incorporated proteins; neutralizing antibodies; Prevention; Target; Cell; Biological receptor; Immunopathology; receptors; Antibody; Glycoprotein; Retroviridae; AIDS; Vaccine; Immune deficiency; Lentivirus; Protein; envelope glycoprotein; Infection; Virus; Medicine; Immunoprophylaxis; Viral disease; Human immunodeficiency virus; Neutralization
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/j.1365-2796.2007.01820.x

. Vaccine‐induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV‐1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV‐1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. HIV‐1 has evolved many mechanisms on the surface of envelope glycoproteins to evade antibody‐mediated neutralization, including the masking of conserved regions by glycan, quaternary protein interactions and the presence of immunodominant variable elements. The primary challenge in the development of an HIV‐1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV‐infected individuals. We also describe the nonvariable cellular receptors involved in the HIV‐1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV‐1 entry.