----- Original Message -----
From: Herman F. Staats, Ph.D.
To: Walter Morton
Sent: Thursday, March 16, 2000 10:09 PM
Subject: Re: Clarification
Walter:
I was able to get this from the links you gave me.
Herman
Bulletin of the World Health Organization
The International Journal of Public Health
More News
Could a nasal spray protect people against human immunodeficiency virus?
Researchers in the USA have received government funding to move ahead with studies of a new approach to vaccinating people against human immunodeficiency virus (HIV) -- not by injection but by a more convenient nasal spray. Bart Haynes and his colleagues at Duke University, North Carolina, have received US$ 5.5 million from the US National Institutes of Health and are hoping to test the approach in rhesus macaques shortly (1).
The announcement came as fresh evidence emerged to stress the urgency of finding a vaccine against HIV. Two further studies published this autumn have emphasized that antiretroviral drugs cannot eradicate HIV from the body, even in individuals who are not known to have a latent reservoir of infection (2,3).
Scientists have long sought to develop a vaccine that could be given without injection because it should be cheaper and easier to administer in developing countries. Also, a vaccine that triggers a strong mucosal immune response may theoretically help to protect against infection with HIV by blocking the virus from entering cells in the genital tract. However, the search has not been straightforward. One key problem has been the adjuvant -- the added constituent that boosts the body's immune response to the immunogen itself. The adjuvant used so far in experimental mucosal vaccines in animals has been cholera toxin, but researchers doubt that this will be acceptable for human vaccines because it can sometimes trigger undesirable side effects. Also, says Herman Staats, a member of the Duke team, cholera toxin may not work as an adjuvant in countries where cholera is endemic.
So the researchers have been testing an alternative adjuvant -- one of the body's own cytokines or messenger chemicals, interleukin-1 (4). The rationale, says Haynes, was to study the cytokines that are stimulated by the presence of cholera toxin, and use these as a short-cut to stimulate a strong response, rather than use cholera toxin itself. Mouse studies have shown that interleukin-1 is effective as an adjuvant for other immunogens, and that vaccines given via the nose can stimulate immune responses in the mucous membranes of the reproductive tract. Although interleukin-1 itself can cause unpleasant symptoms, such as fever and lowered blood pressure, Haynes believes that the dose for a nasal vaccine could be so low that toxicity should not be a problem.
The experimental vaccines to be tested in monkeys are made of synthetic peptides taken from the HIV coat protein gp120, and combine several different strains of the virus to give the greatest possible protection. An experimental vaccine developed by Haynes and his colleagues has already been tested in injected form in people and stimulates antibodies and T cells against the virus. For the tests in macaques, HIV-1 itself cannot be used to challenge the vaccine, as the animals do not become infected by it. Instead, the researchers will use SHIV, an artificial virus made by combining the core of the simian immunodeficiency virus, SIV, with the protein coat of HIV.
A key practical need is to reduce the dose of vaccine, says Haynes: he hopes that using an adjuvant will make this possible. If the monkey studies are successful, the researchers hope that trials of a nasal spray vaccine that uses interleukin-1 as adjuvant may be possible within two years.
1. Duke University Medical Center press release, 19 October 1999 [ news.mc.duke.edu ](http://news.mc.duke.edu/infomatters/news/dumcnews/newsstatic.html).
2. Tae-Wook Chun et al. Re-emergence of HIV after stopping therapy. Nature, 1999, 401: 874?875.
3. Grossman Z et al. Ongoing HIV dissemination during HAART. Nature medicine, 1999, 5: 1099?1104.
4. Staats HF, Ennis FA Jr. IL-1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens. Journal of immunology, 1999, 162: 6141?6147.
I can not open this link either. Their server must be down.
I believe this article is reporting on my publication from last year.
Interleukin 1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens. H.F. Staats and F.A. Ennis, Jr. Journal of Immunology, 162:6141-6147, 1999.
Can you get a copy of my paper? If not, send me a fax number or address and I'll get a copy to you.
Herman
At 07:37 PM 3/16/00 -0500, you wrote:
I found this think to some of your work
google.com
le+Search ) but was unable to access the article.
Do you know what is wrong with this link?
I would like to read more about the nasal spray vaccine.
Thank you,
Walter Morton
Herman F. Staats, Ph.D.
Assistant Research Professor
Departments of Medicine and Immunology
Center For AIDS Research
Box 3307
Duke University Medical Center
Durham, NC 27710
phone: 919-684-8823
fax: 919-684-4288
e-mail: hfs@acpub.duke.edu
duke.edu
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