Immunization with Haemophilus influenzae type b-CRM197 conjugate vaccine elicits a mixed Th1 and Th2 CD4+ T cell cytokine response that correlates with the isotype of antipolysaccharide antibody

Abstract

Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) induces protective antibodies but is T independent and poorly immunogenic in infants. Conjugate vaccines of Hib PS linked to proteins, such as CRM197, increase the PS antibody titer and elicit immunologic memory. To define the conjugate-induced memory T cell response, 19 adults were immunized with Hib-CRM197, and antibody titers, carrier protein-specific CD4+ T cell proliferation, and cytokine production were measured. Hib-CRM197 induced PS and CRM197 antibodies, vigorous T cell recall responses, and production of cytokines, including interleukin (IL)-2, IL-5, IL-10, and interferon-γ. There was marked variability in PS antibody titer, despite consistent CRM197-specific recall responsiveness, which correlated with peak IgM and IgA PS antibody titers. Correlations were also found between IL-2 and IL-5 and IgA PS antibody levels. Hib-CRM197 induced a rapid increase in CRM197-specific memory T cells and mixed Th1/Th2 cytokines, which may regulate the isotype and quantity of PS antibody.