Obstetrics in Brecon

Abstract

Vaccine strategies targeting the earliest stages of HIV infection at the mucosal portal of entry may prevent acquisition. Thus, understanding the immune profiles of mucosal cells after immunization is important for vaccine design. We vaccinated rhesus macaques with replicating Ad5hr-SIV<i>env/gag/nef</i> or empty Ad5hr vector orally/intranasally and intra-tracheally, followed by intramuscular gp120 boosts in alum or alum only. Macaques were repeatedly challenged intravaginally with low doses of SIV_mac251. We evaluated cervicovaginal macrophage (CM) responses to Ad5hr 3d post-immunization, and alveolar macrophage (AM) responses in BAL, as initial immunization was to the upper respiratory tract. CM showed significantly increased expression of the chemokines CCL3 (p&lt;0.01), CCL4, CCL5 and CXCL8 (p&lt;0.0001 for all) after the first prime, which decreased post-2^nd boost. CD4⁺ T-cell frequency in the cervical mucosa was unchanged. CD16 expression was significantly increased post 2^nd Ad and positively correlated with the number of challenges needed for infection (r=0.6763; p=0.0051). Immunization also increased expression of CD16 on AMs up to the 1^st boost time point. Activation of AMs was evident by increased expression of CD40 and CD80 post-2^nd Ad compared to naïve macaques. APRIL expression also significantly increased post-2^nd Ad compared to naive levels and correlated with B cell frequency in BAL (r=0.7329; p=0.0019) and total IgG in BAL-Fluid (r=0.525; p=0.0471). These data indicate that the vaccine regimen did not induce recruitment of susceptible cells to the vaginal mucosa but increased CM CD16 expression associated with delayed SIV acquisition, and further induced AM cytokine expression that may be associated with B cell help.