A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates

• Published in: PloS one 2013-10, Vol.8 (10), p.e78407
• Main Authors: Padte, Neal N, Boente-Carrera, Mar, Andrews, Chasity D, McManus, Jenny, Grasperge, Brooke F, Gettie, Agegnehu, Coelho-dos-Reis, Jordana G, Li, Xiangming, Wu, Douglass, Bruder, Joseph T, Sedegah, Martha, Patterson, Noelle, Richie, Thomas L, Wong, Chi-Huey, Ho, David D, Vasan, Sandhya, Tsuji, Moriya
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adenoviridae - immunology; Adenoviruses; Adjuvants; Adjuvants, Immunologic - pharmacology; Adjuvants, Pharmaceutic - pharmacology; AIDS; Animals; Antibodies, Protozoan - immunology; Antigens; Antigens, Protozoan - immunology; Armed forces; Cancer; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Circumsporozoite protein; Clinical trials; Dendritic cells; Expression vectors; Galactosylceramide; Genetic Vectors - immunology; Glycolipids - immunology; Hepatitis; HIV; Human immunodeficiency virus; Immune response; Immunity; Immunogenicity; Infectious diseases; Lymphocytes; Lymphocytes T; Macaca mulatta - immunology; Malaria; Malaria Vaccines - immunology; Malaria, Falciparum - drug therapy; Malaria, Falciparum - immunology; Male; Medical research; Membrane Proteins - immunology; Monkeys & apes; Pathogens; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - immunology; Primates; Primates - immunology; Priming; Protozoan Proteins - immunology; Replicating; Replication; T cell receptors; Vaccines; Vector-borne diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078407

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.