Systemic immunization with a recombinant Pneumocystis protein vaccine candidate induces systemic and mucosal immune responses in non-human primates (P4260)

Abstract

Abstract Despite widespread antiretroviral therapy, pulmonary disease remains a leading cause of morbidity and mortality in HIV+ patients, likely resulting from increased colonization rates by Pneumocystis (Pc) jirovecii, which causes pneumonia and is associated with chronic obstructive pulmonary disease (COPD). We have previously shown that early detection of antibodies to Pc kexin-like protease (KEX1) in the bronchoalveolar lavage fluid (BALF) correlates with protection from Pc colonization and subsequent COPD development in a macaque model of HIV. Here, we test the capacity of a systemic recombinant KEX1 vaccine to induce detectable KEX1-antibody responses in the lungs. Rhesus macaques (n=6) were intramuscularly (i.m.) immunized with 100ug of truncated, recombinant KEX1 protein + aluminum hydroxide (Alum), rested, then boosted with 50ug of KEX1 + Alum. Mock-immunized macaques (n=6) were injected (i.m.) with proteins from empty E.coli expression vector (pET28b) + Alum. Following boost inoculation, all macaques had plasma KEX1-IgG RET >250,000 (range=256,000-2,000,000) and BALF KEX1-IgG RET >1800 (range=1900-31,800). Five of 6 macaques had detectable BALF KEX1-IgA (range=100-550). Thus, systemic immunization with recombinant protein and Alum results in significant boosting of both circulating and mucosal KEX1 antibody titers. These data support KEX1 as a potent vaccine candidate against Pneumocystis infection.