HIV Vaccine Approaches

Abstract

An HIV (human immunodeficiency virus) vaccine is needed to combat the 1–2 million cases on new HIV infection each year. 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 neutralising 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 HIV, have had limited success. There have been multiple attempts to induce effective immunity to HIV in humans, with only one approach showing partial (31%) efficacy. Several clues on a better path forward have, however, emerged from HIV vaccine trials in humans, studies of humans who naturally control HIV infection and studies in animal models. There has been an improved understanding of anti‐HIV neutralising antibodies, which, if could be induced successfully, are likely to be highly effective. Antibodies that engage Fc receptors on innate immune cells (the so‐called ADCC (antibody‐dependent cellular cytotoxicity) antibodies) have emerged as a key component of successful vaccine strategies. New vaccine design and delivery strategies are now entering large‐scale human efficacy trials. These approaches offer real hope that a safe and effective HIV vaccine will eventually be developed to assist in the control of the HIV/AIDS (acquired immunodeficiency syndrome) pandemic.

Key Concepts

  • A HIV vaccine is urgently needed.
  • There are many hurdles to induce effective HIV immunity.
  • Only one HIV vaccine trial in humans has showed partial efficacy to date.
  • Neutralising antibodies against HIV are highly effective in animal models but are difficult to induce by vaccination.
  • Functional anti‐HIV antibodies that can engage innate immune cells to fight HIV are likely to be a key component of successful HIV vaccine strategies.
  • T‐cell‐based immunity against HIV shows promise in certain settings.
  • New HIV vaccines are entering human efficacy trials.
  • There is considerable promise that an effective HIV vaccine will be developed in the future.

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 non‐neutralising. 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. Neutralising antibodies cannot be detected until 3–6 months after infection. AIDS normally develops in untreated patients after 8–10 years.
Figure 2. Neutralising antibodies bind to HIV Env. HIV Env 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 neutralising 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 recognises carbohydrate domains is also broadly neutralising.
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Further Reading

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Kent, Stephen J(Jun 2017) HIV Vaccine Approaches. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021550.pub3]