From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: Salk and CMI Explained
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6052
Organization: unspecified
Date: Tue, 1 Sep 92 21:43:34 PDT

the San Francisco AIDS Foundation dated August 1992.

Excerpt from OPINION--A Clinician in Amsterdam: Reflections on the 1992 
AIDS Conference, page 28,30, by Mark L. Illeman, FNP

"Jonas Salk announced a new theory that could change the direction of 
vaccine development against HIV and many other diseases. He developed 
the hypothesis after an experiment with monkeys. The monkeys failed to 
resist infection after given an inactivated SI vaccine to induce the 
highest levels of antibodies and cell mediated immunity. Salk reports he 
then realized it was pointless to pursue that path.

"His theory relies on the observation that the first reaction of the 
immune system after infection is among the T cells. This cell mediated 
immunity is called the TH1 response (i.e., the delayed type 
hypersensitivity response of skin inflammation when an antigen is 
injected under the surface.)

"As time after infection increases the other TarmU of the immune system 
swings into action, with the production of antibodies. This humoral 
immunity is called the TH2 response.

"Studies by other groups have suggested to Salk that the way to make a 
vaccine against HIV is to find a way to freeze the immune system in the 
TH1 response.

"A study by Bretschler and colleagues supports this theory. These 
researchers injected the leishmaniasis parasite into a group of mice 
with a small dose of the organism that causes disease, and gave a second 
group a large dose. The first group developed a delayed type 
hypersensitivity reaction only, while the second group had a strong 
antibody response. When challenged with the infectious agent, however, 
only the animals in the first group resisted infection.

"Other researchers have shown that in patients with leprosy, relative 
resistance to the disease is associated with cell mediated immunity, 
while those who produce antibodies are highly susceptible. Work by Gene 
Shearer and colleagues at the National Institutes of Health (NIH) 
supports this theory. They found that individuals who remain HIV 
negative when tested with PCR for HIV infection - despite having been at 
high risk for HIV infection - had good cell-mediated responses against 
HIV, while remaining antibody negative.

"Salk has looked at a cohort of HIV-positive patients who received his 
candidate vaccine by using gamma-irradiated HIV. About half of them had 
a local skin reaction after vaccination, indicating a delayed type 
hypersensitivity reaction. This group has done much better clinically 
than patients who did not respond this way.

"Salk says these data, take together, suggest that the way to make an 
effective vaccine against HIV is to induce a cell-mediated response with 
an extremely low dose of HIV, probably in micrograms. Vaccines that 
induce neutralizing antibodies are directed against cell-free virus. But 
HIV is different, similar to an intracellular parasite.

"Salk feels that if this approach works, it would be applicable to 
vaccines for other parasitic diseases. The goal now is to find out how 
to lock in the cell-mediated reaction so that the subsequent production 
of antibodies is prevented. Salk is conducting studies to determine 
which immunogens and adjuvants to use, and at what dosages and dosing 
intervals."