Induction of Protective Mucosal Antibodies, T Cells, and β Chemokines

Mucosal transmission of HIV is responsible for the rectal, vaginal, male genital, and possibly oral routes of infection. With the identification of coreceptors in HIV/SIV binding and fusion a new approach has been opened in HIV/SIV transmission and protection. Mucosally targeted vaccination aims to elicit secretory IgA and IgG antibodies at the mucosal surface and CD4 ⁺ and CD8 ⁺ T cell functions in the mucosal tissues, the draining iliac lymph nodes, and the circulating blood. In addition, however, β chemokines may be induced, especially by stimulating CD8 cells, and these inhibit HIV/SIV replication by blocking CCR-5 receptors expressed on the surface of CD4 ⁺ T cells. Immunization of macaques by targeting the rectal mucosa draining iliac lymph nodes (TLN) with SIV gp120 and p27 antigens was followed by rectal challenge with the SIVmac 32H J5 molecular clone. Total protection was induced in 4 of 7 macaques, compared with infection in 13 of 14 macaques unimmunized or immunized by other routes ( p = 0.025). The remaining three macaques showed a decrease in viral load (>90%), indicating that all seven TLN-immunized macaques showed total or partial protection ( p = 0.001). Protection was associated with an increase in the iliac lymph nodes of IgA antibody-secreting cells to p27 ( p < 0.02) rectal, urinary, and serum IgA and IgG antibodies, and T cell-proliferative responses to gp120 and p27. However, the most significant association was found between protection and CD8-suppressor factor ( p < 0.01), the β chemokines RANTES ( p < 0.01), MIP-1β ( p < 0.01), and possibly MIP-1α in the iliac lymph nodes. The coreceptor CC-R5 is also found in simian CD4 ⁺ T cells and SIV replication in these cells can be inhibited by the β chemokines. Immunization against mucosal transmission of SIV/HIV can not be broadened to elicit, in addition to sIgA and IgG and cytotoxic CD8 cells, CD8-SF and the integral chemokines in the mucosal tissues and the inductive iliac lymph nodes.