Evolution of antibody responses against carbohydrate and protein antigens of Pneumocystis carinii: Implications for antibody-based vaccine protection (51.12)

Abstract

Abstract Pneumocystis (PC) pneumonia is a leading opportunistic infection among HIV+ individuals. Mice deficient in CD4+ T cells or B cells are susceptible to PC pneumonia, yet adoptive transfer of serum from PC challenged mice can prevent PC pneumonia. To evaluate factors critical for antibody-based resistance against PC, we assessed antibody responses to intratracheal PC challenge in Balb/c mice. The kinetics of anti-PC Ig induction are prolonged, peaking after the majority of PC is cleared from the lungs. Low anti-PC IgM titers(1:120) exist at baseline and are enhanced by vaccination(1:2600), and the induced anti-PC IgM is strongly cross-reactive with zymosan. Anti-PC IgG is absent at baseline but is rapidly induced through day 36 post-challenge (titer 1:38,000). We assessed the evolution of Igs directed against the PC cellular wall carbohydrates β-glucan and chitosan, which may potentially elicit B cell responses in a CD4+ T cell independent manner. Baseline IgM directed against the PC cellular wall antigen β-glucan is high, rapidly enhances 2 days post challenge (titer 1:5000), and diminishes, suggesting a potential role for B1 cells in this response, while PC induces anti-β-glucan IgG (titer 1:1000) with a significantly delayed timecourse, peaking at day 42 post-challenge; IgM and IgG responses directed against chitosan manifest similar kinetics. Finally, mice exposed to PC and subsequently depleted of CD4+ T cells after the primary response with the antibody GK1.5, mount similar boosting responses to CD4+ T cell intact mice. Our studies suggest that PC elicits antibodies against protein and carbohydrate antigens, implicating B1 and B2 cells in these responses, and suggest that components of anti-PC B cell memory may be maintained under CD4+ T cell deficiency.