HIV Vaccine Approaches

Abstract

The goal of vaccination is to establish long‐term immunological readiness that allows rapid protection against infectious disease. All current successful vaccines achieve this by inducing neutralizing antibodies, which are effective against acute, cytopathic infections that could otherwise prove fatal. By contrast, potential vaccines against highly variable pathogens that establish persistent infections, such as human immunodeficiency virus (HIV), have had limited success. Responses in addition to neutralizing antibodies, directed to specific anatomical locations, are probably necessary. Human studies on HIV‐exposed/infected long‐term nonprogressors to acquired immunodeficiency syndrome (AIDS) are beginning to reveal the correlates of immune protection that new vaccines should attempt to reproduce. Coupled with exciting new vaccine design and delivery strategies, these novel HIV vaccine approaches offer real hope that the HIV/AIDS pandemic can finally be overcome.

Keywords: HIV; AIDS; vaccination; correlates of immune protection; vaccine strategies

Figure 1.

The course of HIV infection. After initial exposure, viral load reaches a peak at 3–4 weeks. CD4+ T cells decline but recover quickly on initiation of adaptive immune responses. This response includes cytotoxic T cells which probably control viral load. Antibodies to the viral envelope are also detected, but are nonneutralizing. These antibodies are capable of complement‐mediated attack but their role in controlling viraemia is unclear. Viral load continues to decline until it reaches a ‘set point’; a good correlate of subsequent disease progression. Neutralizing antibodies cannot be detected until 3–6 months after infection. AIDS normally develops in untreated patients after 8–10 years.

Figure 2.

Neutralizing antibodies bind to HIVEnv. HIVEnv binds to CD4 and a coreceptor (usually either CXCR4 or CCR5) to gain entry to target cells. A schematic enlargement of the envelope glycoprotein is shown. The Env glycoprotein contains epitopes for broadly neutralizing monoclonal antibodies b12, 4E10 and 2F5 as well as those induced after CD4 binding. The variable regions are shielded with carbohydrate moieties shown. A monoclonal antibody 12G5 that recognizes carbohydrate domains is also broadly neutralizing.

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McKnight, Á, and Pennington, Daniel J(Dec 2009) HIV Vaccine Approaches. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021550.pub2]