Live attenuated SIV vaccines provide robust protection against subsequent challenge by parenteral and mucosal routes. I will discuss some of the correlates of the maturation of protection conferred by vaccination with SIV with a deleted nef gene against subsequent high dose vaginal challenge in the SIV-rhesus macaque model of HIV-1 transmission to women. In this model, vaccination profoundly affects the early events in transmission of establishing and expanding a small founder population of infected cells in the transition zone and adjoining endocervix. The 106-fold reduction in viral load (VL) at this site is associated with prevention or attenuation of systemic infection. I will discuss the relationship of these effects to mechanisms to deliver IgG antibodies at mucosal frontlines through local production and concentration by Fc-receptor mediated mechanisms operating in mucosal epithelium.
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