TAT Protein for preventing or treating AIDS

Abstract

The invention relates to a method of preventing or treating acquired immunodeficiency syndrome (AIDS) in a patient, wherein the patient is administered with a Tat protein comprising amino acid sequence SEQ ID NO: 1 or 2, or a variant thereof capable of stimulating an immune response against Tat proteins.

Description

[0001]The present invention provides compositions and methods for preventing or treating acquired immunodeficiency syndrome (AIDS) in a human patient, and a vaccine against an HIV-infection.TECHNICAL BACKGROUND[0002]The search for a vaccine against AIDS remains a major issue since the discovery of the HIV-1 (Barre-Sinoussi et al., 1983). The failure of classical vaccine approaches targeting the HIV-1 envelop proteins points out the interest to use another target such as the HIV-1 trans-activator of transcription protein called Tat, due to its extra cellular function involving the collapse of the immune cellular response against HIV infected cells (Jeang et al., 1999).[0003]Tat exists predominantly in two different lengths, 86-87 residues or 99-101 residues, that display multifaceted activities (Jeang et al., 1999). The long forms are predominant in clinical isolates from all HIV-1 subtypes except subtype D, due to the presence of a non-synonymous single nucleotide polymorphism, crea...

AI Technical Summary

Benefits of technology

The invention provides a method for preventing or treating acquired immunodeficiency syndrome (AIDS) in a patient by administering a protein or a variant that stimulates an immune response against Tat proteins. The protein or variant is capable of stimulating an immune response against at least five HIV-1 subtypes. The invention also provides a vaccine comprising the protein or variant as an active ingredient. The method and vaccine can be used to immunize warm-blooded animals against AIDS. The protein or variant is a Tat Oyi protein that has been modified to include a cysteine at position 22, which strengthens its immunogenicity. The invention also includes a method for detecting anti-Tat IgG in patients' blood samples.

Problems solved by technology

However, seropositive patients that have antibodies against Tat are unable to recognize Tat variants from all HIV-1 subtypes (Campbell et al., 2007b).

Moreover, these antibodies fail to slow disease progression to AIDS (Senkaali et al., 2008).

Moreover, a Tat vaccine using a B subtype Tat has also a low probability to provide a therapeutic and a preventive effect even in Europe and North America due to the incapacity of the immune system to neutralize extra cellular Tat.

However, clinical trials were not successful (Vanichseni et al., 2004).

It is important to note that immunization with the B subtype Tat Bru does not stimulate an efficient response against Tat variants from A and C HIV-1 subtypes that corresponds to 75% of the contamination in the world (Opi et al., 2002).

This result outlines again how mutations in Tat variants can affect immunogenicity but it shows also that a large amount of seropositive patients are unable to recognize Tat.

However, the paradox is that the CD8 T cell response in EPS Kenyan sew workers is five time lower in magnitude than that of seropositive Kenyan sex workers who ultimately develop AIDS (Alimonti et al., 2006).

Moreover, SHIV infected cells were no longer detectable at 8 weeks post-challenge in Tat Oyi vaccinated macaques.

This goal has never been achieved in seropositive patients under HAART treatment.

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