Short communication: rapid preparation of preventive and therapeutic whole-killed retroviral vaccines using the microbicide taurine chloramine.
A current urgent priority is to develop microbicides and vaccines to combat retroviruses like human immunodeficiency virus (HIV). We show that the cysteine-selective natural compound, taurine chloramine (T-NCl), can be effective in this task. A number of proteins in all retroviruses contain highly conserved cysteine-rich regions that are essential for infection and replication. Our data show that by targeting these essential cysteine residues, T-NCl (2 or 5 mM) acts as a highly effective and safe microbicide that fully blocks the infectivity of high HIV-1 titers (10(6) TCID(50) units/ml) but is not injurious to eukaryotic cells. We also demonstrate that T-NCl can be used to prepare a highly effective whole-killed vaccine against murine AIDS (MAIDS) that shows both preventive and therapeutic efficacy. The vaccine consists of a T-NCl-inactivated retrovirus suspension in host cell lysate. The novelty of our approach lies in the ease and speed of vaccine preparation and its avoidance of harsh inactivation or purification steps that can alter native viral conformation. Our approach is therefore likely to overcome a number of intractable obstacles to the preparation of an effective whole-killed HIV vaccine, such as surviving infective viral particles, rapid viral mutation rates, numerous viral strains, and harsh purification steps. Our approach may also permit the rapid preparation of autologous, or custom-made, vaccines for individual patients.
Dudani
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AK
Centre for Biologics Research, Biologics and Genetic Therapies Directorate, Sir Frederick Banting Research Centre, Ottawa, Ontario, Canada K1A 0L2.
Martyres
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A
Fliss
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D016915:AIDS Vaccines / Q000008:administration & dosage / Q000302:isolation & purification*; D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007115:Immunization Schedule; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000821:virology; D013654:Taurine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D014611:Vaccination; D038301:Virus Inactivation / Q000187:drug effects; D014779:Virus Replication
D016915:AIDS Vaccines; D000998:Antiviral Agents; D013654:Taurine; C043410:N-chlorotaurine