title: Alpha-C-galactosylceramide as an adjuvant for a live attenuated influenza virus vaccine.
abstract: There is a substantial need to develop better influenza virus vaccines that can protect populations that are not adequately protected by the currently licensed vaccines. While live attenuated influenza virus vaccines induce superior immune responses compared to inactivated vaccines, the manufacturing process of both types of influenza virus vaccines is time consuming and may not be adequate during a pandemic. Adjuvants would be particularly useful if they could enhance the immune response to live attenuated influenza virus vaccines so that the amount of vaccine needed for a protective dose could be reduced. The glycolipid, alpha-galactosylceramide (alpha-GalCer), has recently been shown to have adjuvant activity for both inactivated and replicating recombinant vaccines. The goal of these experiments was to determine whether a derivative of alpha-GalCer, alpha-C-galactosylceramide (alpha-C-GalCer) can enhance the immune response elicited by a live attenuated influenza virus vaccine containing an NS1 protein truncation and reduce the amount of vaccine required to provide protection after challenge. Our results indicated that the adjuvant reduced both morbidity and mortality in BALB/c mice after challenge with wild type influenza virus. The adjuvant also increased the amount of influenza virus specific total IgG, IgG1, and IgG2a antibodies as well as IFN-gamma secreting CD8(+) T cells. By using knockout mice that are not able to generate NKT cells, we were able to demonstrate that the mechanism of adjuvant activity is dependent on NKT cells. Thus, our data indicate that stimulators of NKT cells represent a new avenue of adjuvants to pursue for live attenuated virus vaccines.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029-6574, United States.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Kopecky-Bromberg
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Fraser
authors.forename: Natalie
authors.initials: N
authors.lastname: Pica
authors.forename: Elena
authors.initials: E
authors.lastname: Carnero
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Moran
authors.forename: Richard W
authors.initials: RW
authors.lastname: Franck
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002642:Chick Embryo; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012720:Severity of Illness Index; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D005699:Galactosylceramides; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; C493154:alpha-galactosylceramide; D007371:Interferon-gamma