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Vol 51(2017) N 6 p. 819-829; DOI 10.1134/S0026893317060176 Full Text

A.N. Vzorov*, L.V. Uryvaev

Requirements for the Induction of Broadly Neutralizing Antibodies against HIV-1 by Vaccination

Ivanovsky Institute of Virology, Gamaleya Federal Research Center of Epidemiology and Microbiology, Moscow, 123098 Russia

*avzorov@mail.ru
Received - 2017-03-26; Accepted - 2017-04-18

A study of the induction of broadly neutralizing antibodies (bNAbs) in HIV-infected patients and vaccinated subjects revealed the main criteria for the formation of bNAbs (the duration of exposure to a viral antigen, the effect of the diversity of HIV variants, and the removal of barriers associated with the Env-dependent defense mechanisms of HIV-1). Modified trimers of the HIV-1 envelope protein (Env) exposed on virus-like particles (VLP) have unique properties: they (i) modulate the exposure of binding sites (bs) of the CD4 receptor and co-receptor; (ii) create steric restrictions for contact with bNAbs; (iii) increase the Env presentation density, thus enhancing the immune response; (iv) form stable trimers that do not induce off-target immune responses; and (v) allow additional modifications to their structure and construction of a platform with immunostimulating molecules. Immunization using a heterologous subtype-cross prime-boost regime with modified trimeric Env is capable of inducing somatic hypermutation levels necessary for the formation of bNAbs.

HIV-1, broadly neutralizing antibodies, protective neutralizing antibodies, Env trimer, virus-like particles



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