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  • Review Article
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Vaccines

New hope for an aids vaccine

Nature Reviews Immunology volume 2, pages 239–250 (2002)Cite this article

Key Points

  • The development of an AIDS vaccine is an important challenge, because it is not easy to raise neutralizing antibodies, HIV is able to form latent proviral DNA and the virus is highly variable.

  • Current vaccine development uses DNA and live-virus vectors to raise T-cell, as well as antibody, responses.

  • Recent successes include DNA–virus prime–boost protocols using recombinant modified vaccinia Ankara (rMVA) and adenovirus 5 (Ad5) DNA as a prime and virus vectors as boosters.

  • To date, it has proven difficult to define a single correlate of protection with which to assess the relative success of monkey trials for HIV vaccines.

  • Several HIV vaccines are now in phase I/II trials, but it will take at least another five years for any of these vaccines to be ready for human use, even on the most optimistic timescale.

Abstract

The twenty-first century has begun with considerable success for new AIDS vaccines in macaque models. A common feature of these vaccines is their ability to induce high-frequency CD8+ T-cell responses that control, rather than prevent, infection with HIV. The new vaccines, which include DNA vaccines and live viral vectors, are based on technologies that have been developed since the start of the AIDS epidemic. The ultimate promise of these vaccines will be realized only when efficacy trials in humans are conducted.

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Figure 1: Structure of HIV-1.
Figure 2: Genetic relationships of HIV-1 subtypes and circulating recombinant forms.
Figure 3: Two strategies for HIV DNA vaccine inserts.
Figure 4: Different patterns of immune responses, but similar patterns of SHIV-89.6P control in DNA–rMVA and rMVA-only immunized animals.

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Acknowledgements

I would like to thank B. Moss, H. Ertl, T. Mastro and R. Amara for critical comments. I am indebted to R. Amara for help with Table 2 and to J. Smith for help with Fig. 4, and I would like to thank H. Drake-Perrow for expert administrative assistance. This work was supported in part by Integrated Preclinical/Clinical AIDS Vaccine Development Program projects, the Emory/Atlanta Center for AIDS Research and Yerkes Regional Primate Research Center.

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  1. Vaccine Research Center and Yerkes Primate Research Center of Emory University, 954 Gatewood Drive, NE, Atlanta, 30329, Georgia, USA

    Harriet L. Robinson

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  1. Harriet L. Robinson
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Related links

Related links

DATABASES

Entrez

human adenovirus 5

SHIV

vaccinia Ankara

LocusLink

IL-1

IL-2

IL-6

IL-12

IFN-α/β

IFN-γ

TNF

FURTHER INFORMATION

Encyclopedia of Life Sciences

HIV

HIV life-cycle and inherited co-receptors

HIV Molecular Immunology Database

HIV Vaccine Trials Network

IAVI Database of Preventitive AIDS Vaccines in Human Trials

Nature's AIDS Insight

UNAIDS

Vaccine Research Center

Glossary

ISOLATE

An isolate of HIV-1 is a population of virus that has been recovered from a patient. Isolates that have been distributed to other laboratories are sometimes called strains.

SUBTYPES OF HIV-1

These are genetically related clusters of HIV-1. Subtypes of HIV-1 are also called clades. They do not fall into specific categories based on their susceptibility to neutralizing antibody.

DNA VACCINE

A DNA plasmid that expresses the immunizing protein. Vaccination is accomplished by uptake and expression of the DNA by cells in the vaccinated host.

ADJUVANT

Adjuvants are substances that, when added to an immunogen, increase the immune response to that immunogen. Genetic adjuvants are DNAs that encode a molecule that augments an immune response.

LONG-TERM NON-PROGRESSORS

HIV-1-infected humans who enjoy many years of productive life. Long-term non-progressors typically have levels of viral RNA in their blood of less than 1000 copies per ml.

CODON OPTIMIZATION

Changing the codons for an amino acid to those most frequently used in human cells.

MICROSPHERE

A carrier for a vaccine that facilitates immune responses by stabilizing and/or increasing the uptake of the vaccine.

HELPER CELL

A cell line that provides essential viral functions for the growth of a defective viral vector.

PRIME–BOOST

When a single application of a vaccine is insufficient, repeated immunizations are carried out using the same vaccine preparation (homologous prime–boost) or using different vaccine preparations (heterologous prime–boost) to sequentially stimulate a better immune response.

GENE GUN

A device that uses compressed helium to bombard DNA-coated gold beads into cells. The beads are usually 1–2 μm in diameter.

TH1/TH2

(T-helper cells type 1 and T-helper cells type 2). These two types of T cell have distinctive patterns of lymphokine production. In mouse models, TH1 cells produce IFN-γ (which supports the production of complement-dependent antibodies and the activation of phagocytic defences), whereas TH2 cells produce IL-4 (which supports the production of complement-independent antibodies and the activation of eosinophils and mast cells).

VIRAL SET POINT

The viral set point is the steady-state level of viral RNA that is established following the acute phase of infection. At present, viral set points are the best known indicators for how rapidly a patient will progress to AIDS.

CORRELATE OF PROTECTION

An immune response that indicates that a vaccine will protect against a challenge infection.

NON-TRANSMITTERS

HIV-1-infected humans who do not transmit their infection through homosexual or heterosexual activity. These individuals typically have levels of viral RNA in their blood of <1000 copies per ml.

SUBUNIT VACCINE

Subunit vaccines encode portions of a pathogen only.

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Robinson, H. New hope for an aids vaccine. Nat Rev Immunol 2, 239–250 (2002). https://doi.org/10.1038/nri776

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