title: A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.
abstract: A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP) model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA), consists of two non-replicating recombinant adenoviral (Ad) vectors, one expressing the circumsporozoite protein (CSP) and another expressing the apical membrane antigen-1 (AMA1) of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM) immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold) in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, New York, United States of America.
authors.forename: Neal N
authors.initials: NN
authors.lastname: Padte
authors.forename: Mar
authors.initials: M
authors.lastname: Boente-Carrera
authors.forename: Chasity D
authors.initials: CD
authors.lastname: Andrews
authors.forename: Jenny
authors.initials: J
authors.lastname: McManus
authors.forename: Brooke F
authors.initials: BF
authors.lastname: Grasperge
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Jordana G
authors.initials: JG
authors.lastname: Coelho-dos-Reis
authors.forename: Xiangming
authors.initials: X
authors.lastname: Li
authors.forename: Douglass
authors.initials: D
authors.lastname: Wu
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Bruder
authors.forename: Martha
authors.initials: M
authors.lastname: Sedegah
authors.forename: Noelle
authors.initials: N
authors.lastname: Patterson
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Sandhya
authors.initials: S
authors.lastname: Vasan
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology; D006017:Glycolipids / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology; D011323:Primates / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D006017:Glycolipids; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium