* Equal contribution

Abstract:

It is generally assumed that the most effective way to control the AIDS epidemic will be the use of a vaccine that protects against HIV-1 infection 1. For most viruses, neutralizing antibodies (NAbs) elicited by currently available vaccines are a correlate of protection 2, 3. Passive immunization was shown to confer protection against SIV infection in macaque models 4-9, suggesting that pre-existing humoral immunity may also be able to prevent HIV-1 infection. However, the development of an effective NAb-based vaccine has been hampered by the huge sequence variability of HIV-1. An important focus of vaccine design is therefore the identification and characterization of antibody specificities that are effective against the majority of currently circulating HIV-1 variants in order to use their epitopes for immunogen design 10. However, the mimicking of epitopes of cross-reactive neutralizing antibodies in an immunogen have only met very limited success 11. During natural HIV-1 infection, NAbs against autologous viral strains are not detectable until approximately two months or later after transmission 12-20. One of the factors involved in this delayed development of NAbs is the massive depletion of CD4+ T cells and destruction of germinal centers in the gut during acute HIV-1 infection 21, 22. This early loss of germinal centers may have an effect on the generation of early highaffinity HIV-1-specific NAbs. Nevertheless, a substantial proportion of HIV-infected individuals (~ 30%) is able to mount NAb responses against a wide range of heterologous HIV-1 variants after two to three years of infection 23-25. Thus far, several rare potent monoclonal …

Año de publicación:

2012

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Fuente:

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