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Vaccine Advance: Monkeys Still Infected, But Protected from Illness.



On October 20 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 HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. , 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 DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 which coded for certain proteins from the virus; in the body, the DNA produces those proteins, so that the immune system immune system

Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders.
 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 IL2 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 See control key.

1. CTL - Checkout Test language.
2. CTL - Compiler Target Language.
3. CTL - Computational Tree Logic
 (cytotoxic T lymphocyte cytotoxic T lymphocyte CTL, cytotoxic T cell Immunology A subset of T cells with a CD8 receptor on the surface that recognizes and lyses malignant or virally-infected self cells bearing self, ie 'haplotype restricted', class I MHC molecules. ) response after infection, stable CD4+ counts (T-cell counts), and CD4+ T cells T cells
A type of white blood cell produced in the thymus gland. T cells are an important part of the immune system. Infants born with an underdeveloped or absent thymus do not have a normal level of T cells in their blood.
 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 Both an international and regional referral center, Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a major teaching hospital of Harvard Medical School. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and  at Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , and at Merck Research Laboratones.

Comment

This test shows for the first time that an HIV vaccine HIV vaccine AIDS As of mid-2005, there is no viable anti-HIV vaccine. See AIDS.  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 pus, thick white or yellowish fluid that forms in areas of infection such as wounds and abscesses. It is constituted of decomposed body tissue, bacteria (or other micro-organisms that cause the infection), and certain white blood cells.  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 viremia /vi·re·mia/ (vi-re´me-ah) the presence of viruses in the blood.

vi·re·mi·a
n.
The presence of viruses in the bloodstream.
 and prevention of clinical AIDS in rhesus monkeys by cytokine Cytokine

Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine).
 augmented DNA vaccination. Science. October 20, 2000; volume 290, number 5491, pages 486-492.
COPYRIGHT 2000 John S. James
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Author:James, John S.
Publication:AIDS Treatment News
Geographic Code:1USA
Date:Oct 20, 2000
Words:746
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