title: Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate.
abstract: Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum. Currently, the conjugate vaccine Pfs25-EPA/Alhydrogel is in Phase 1 clinical trials in the USA and Africa. Thus far, it has proven to be safe and immunogenic, but it is expected that a more potent formulation will be required to establish antibody titers that persist for several malaria transmission seasons. We sought to determine the contribution of carrier determinants and adjuvants in promoting high-titer, long-lived antibody responses against Pfs25. We found that both adjuvants and carrier proteins influence the magnitude and capacity of Pfs25-specific humoral responses to remain above a protective level. Furthermore, a liposomal adjuvant with QS21 and a TLR4 agonist (GLA-LSQ) was especially effective at inducing T follicular helper (Tfh) and LLPC responses to Pfs25 when coupled to immunogenic carrier proteins.
authors.affiliation: Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Radtke
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Anderson
authors.affiliation: Laboratory of Parasitic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Riteau
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Rausch
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD, USA.
authors.forename: Puthupparampil
authors.initials: P
authors.lastname: Scaria
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Kelnhofer
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Randall F
authors.initials: RF
authors.lastname: Howard
authors.affiliation: Laboratory of Parasitic Diseases, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.affiliation: Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Duffy
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D045142:Cross-Priming / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D017780:Malaria Vaccines; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins