Use of new CD4-Ig antibody as a potential candidate for generating HIV-1 effective vaccine Student name:
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1 .      Introduction The HIV-1 virus causes over 1.5 million deaths worldwide each year and already infected over 110 milion people since it was identified in 1982. Antiretroviral therapy has reached over 11 million people and allows many HIV-1-infected people a long lifespan. However, the life-long chemotherapy is not without side effects and the cancer burden and other fatal illnesses among infected individuals remains elevated. Despite the fact that HIV-1 was first identified more than 30 years ago, prospects for a highly effective licensed HIV-1 vaccine seem remote.
 High genetic variability, its ability to escape adaptive immunity and the absence of distinct immune correlates of protection are factors that present real challenges for vaccine development. Understanding the mechanisms underlying the origin and antigenic specific of antibodies that efficiently neutralize a wide range of HIV-1 subtypes is crucial to developing a successful HIV-1 vaccine.
a.      Infection cycle The HIV-1 infection cycle begins with host cell recognition and entry mediated by the HIV-1 envelope spike (Env) on the surface of the virion. Each Env is composed of a trimer of identical gp160 protein subunits that are cleaved post translationally to yield two associated glycoproteins- gp120 and gp41. Gp120 carries the recognition sites for the host receptor (CD4) and coreceptor (CCR5 and CXCR4)and gp41 mediates fusion between the virus and host cell membranes. Although the immune system does respond to the infection by generating different types of antibodies, HIV-1 mutates at a sufficiently high rate and produces enough diversity in the viral population that the viral swarm in any infected person appears to contain resistant variants to any developing antibody (Wei, Decker et al. 2003).  The result is a continuing race between newly developing antibodies and the rapidly mutating virus, which ultimately leads a small percentage of HIV-1 infected individuals to produce antibodies that can neutralize a broad range of different viral strains (Mikell, Sather et al. 2011, Moore, Gray et al. 2012).    b.      HIV-1
challenges As mentioned above, structural and biophysical studies have revealed as number of features of Env that enable HIV-1 to evade the human antibody response. Remarkably common in the set of resistant variants are those that add or remove potential N-linkd glycosylation sites (Wei, Decker et al. 2003). The many glycans decorating the surface of Env form a "shield" that reduces access to protein epitopes. These glycans have the same chemical structures found on host glycoproteins, and individually they are therefore indistinguishable from the host, impeding development of uniquely glycan-specific anti-HIV antibodies.
Immune ….