Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine.

Abstract

Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine. MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell responses, and protection in CD4KO mice, which were comparable to those in WT mice. In contrast, Alum adjuvant effects were dependent on CD4+ T cells. MPL+Alum adjuvant was effective in recruiting monocytes and neutrophils as well as in protecting macrophages from Alum-mediated cell loss at the injection site in CD4KO mice. MPL+Alum appeared to attenuate MPL-induced inflammatory responses in WT mice, likely improving the safety. Additional studies in CD4-depleted WT mice and MHC class II KO mice suggest that MHC class II+ APCs contribute to providing alternative B cell help in the CD4-deficient condition in the context of MPL+Alum-adjuvanted vaccination.