Vaccine Advance: Monkeys Still Infected, but Protected from Illness

On October 20, 2000 researchers reported that a modern high-tech vaccine protected all monkeys vaccinated from becoming ill from an HIV-like virus, while half of the control monkeys given a sham vaccine instead had died of the infection by day 140.⁽¹⁾ This careful, well-designed experiment was important in showing that vaccination can protect against HIV, and in illustrating which immune mechanisms seem to be protective. But this vaccine technology is far from ready for human use -- for example, the virus it protected against was exactly the same virus used to make the vaccine, while humans would have to be protected from a variety of HIV strains.

This vaccine used DNA which coded for certain proteins from the virus; in the body, the DNA produces those proteins, so that the immune system can be prepared to respond if it encounters the real virus later. In this experiment, the vaccination was given as four doses (at weeks zero, four, eight, and 40); at weeks zero and four, some of the monkeys were also given IL-2, either by a similar DNA vaccine coded to produce IL-2, or simply by injection.

At week 46 the monkeys were given a large dose of virus intravenously. All of the animals, vaccinated or not, became infected. But all of the animals that were vaccinated and received the IL-2 did not show disease progression, either clinically or by laboratory measures such as T-cell count. Their virus was well controlled, either below the limit of detection of the test or close to the limit for those that received the IL-2 by DNA technology, or under a thousand copies in those that received the IL-2 by injection (which also worked, but not as well). But the control animals who did not receive any protection had peak viral loads of 10 million or higher, and setpoint viral loads of about a million copies. (The animals that received the DNA vaccine but without any IL-2 had mixed results. And even though the IL-2 was given only at weeks zero and four, it had clear immune benefits over 10 months later, when the animals were last measured.)

The vaccinated animals had good CTL (cytotoxic T lymphocyte) response after infection, stable CD4+ counts (T-cell counts), and CD4+ T cells that responded specifically to the infecting virus. The unprotected animals had weak CTL response, rapidly falling T-cell counts, and no virus-specific CD4+ T cell responses. The vaccinated animals had no neutralizing antibodies before infection -- suggesting that the cellular immune responses, not the antibodies, were important for initial protection; but neutralizing antibodies did develop by day 21 after infection, so they might also have helped control the virus. (The unvaccinated animals could not generate neutralizing antibodies because they had lost their T-cell responses to the virus.)

The researchers who did this study were mostly at Beth Israel Deaconess Medical Center at Harvard Medical School, and at Merck Research Laboratories.

Comment

This test shows for the first time that an HIV vaccine can work to prevent illness. While this vaccine did not prevent HIV infection, it made the infection much less severe. Besides the benefit to the individual, such a vaccine could have important public-health benefits in controlling the epidemic, as persons with an undetectable or very low viral load are likely to be much less infectious than those with viral loads thousands of times higher.

It is not known if such a vaccination strategy could help those already infected -- but animal tests might give a preliminary answer quickly. In any case the data from this study will indirectly help persons with HIV, by providing confirmation and additional information about what immune responses are protective. Any therapy (vaccine or otherwise) that restores those responses in HIV-positive patients who have lost them should get more attention.

This report should also alert those interested that we are in the middle of a revolution of vaccine technology -- with enormous potential for improving health, especially in developing countries, if it is applied. For example, the traditional smallpox vaccine was basically dried pus from scabs on a calf -- and adjuvants (chemicals which somehow made vaccines work better) were discovered by trial and error or not at all. The technology now being developed will permit the creation of rationally designed vaccines made to order for specific needs.

References

1. Barouch DH, Santra S, Schmitz JE, and others. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. SCIENCE. October 20, 2000; volume 290, number 5491, pages 486-492.

ISSN # 1052-4207

Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.

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