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 Method of eliciting anti-HIV-1 helper T cell responses

Details
Inventors: Walker, Bruce D.;
Assignee: The General Hospital Corporation (Boston, MA)
Primary Examiner: Stucker; Jeffrey
Assistant Examiner:
Attorney, Agent or Firm: Fish & Richardson P.C.

A method of producing an HIV-specific helper T cell response in an animal by (1) providing a polypeptide 8 to 50 amino acid residues in length and having a helper T cell epitope of a HIV-1 p24 peptide; and (2) administering to the animal an amount of the polypeptide sufficient to produce an HIV-specific helper T cell response.

DETAILED DESCRIPTION A number of HIV-1 p24 peptides that elicit HIV-1-specific helper T cell responses have been identified.
Contemplated within the scope of this invention are methods of administering p24 peptides, vectors encoding such peptides, and cells containing such vectors to animals suspected of being infected by HIV.
The peptides were discovered in the course of studying a subset of HIV-1 infected persons who have successfully controlled virus replication in the absence of antiretroviral therapy.
Despite infections of up to 18 or more years, these individuals maintain normal CD4+ T cell counts and low to undetectable viral loads, and have no evidence of HIV-1 related disease manifestations (Haynes et al.
, Science 271:324-328 [1996]).
Such individuals with long term non-progressive infection were examined for evidence of CD4+ helper T cell responses directed against HIV-1.
All amino acid sequence numberings are as described in Myers et al.
, Human Retroviruses and AIDS, 1990: A compilation and analysis of nucleic acid and amino acid sequences (1990).
EXAMPLE 1 Anti-HIV-1 Helper T cell Responses in HIV-1-Infected Individuals.
Initial studies were performed in an HIV-1 infected hemophiliac (subject 161-J) with 18 years of documented seropositivity, a normal CD4+ T cell count, and undetectable viral load (<400 RNA molecules/ml), who had never been treated with antiretroviral agents.
To determine the CTL memory response for this individual, peripheral blood mononuclear cells (PBMC) were cultured at 250 to 16,000 cells per well in 24 replicate wells of a 96-well microtiter plate.
To each well, 2.
5.
times.
10.
sup.
4 gamma-irradiated (30Gy) PBMC from an HIV-1 seronegative donor were added, along with CD3-specific monoclonal antibody 12F6 at 0.
1 .
mu.
g/ml.
14 days later, wells were split and assayed for cytotoxicity on .
sup.
51 Cr labeled autologous B-lymphocytes infected with vaccinia-expressing HIV-1 gene products.
The fraction of nonresponding wells was defined as the number of wells in which



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