title: A novel respiratory syncytial virus (RSV) F subunit vaccine adjuvanted with GLA-SE elicits robust protective TH1-type humoral and cellular immunity in rodent models.
abstract: BACKGROUND
  Illness associated with Respiratory Syncytial Virus (RSV) remains an unmet medical need in both full-term infants and older adults. The fusion glycoprotein (F) of RSV, which plays a key role in RSV infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing RSV-specific immunity.
  
  
  RESULTS
  BALB/c mice and cotton rats, two well-characterized rodent models of RSV infection, were used to evaluate the immunogenicity of intramuscularly administered RSV vaccine candidates consisting of purified soluble F (sF) protein formulated with TLR4 agonist glucopyranosyl lipid A (GLA), stable emulsion (SE), GLA-SE, or alum adjuvants. Protection from RSV challenge, serum RSV neutralizing responses, and anti-F IgG responses were induced by all of the tested adjuvanted RSV sF vaccine formulations. However, only RSV sF + GLA-SE induced robust F-specific TH1-biased humoral and cellular responses. In mice, these F-specific cellular responses include both CD4 and CD8 T cells, with F-specific polyfunctional CD8 T cells that traffic to the mouse lung following RSV challenge. This RSV sF + GLA-SE vaccine formulation can also induce robust RSV neutralizing titers and prime IFNγ-producing T cell responses in Sprague Dawley rats.
  
  
  CONCLUSIONS
  These studies indicate that a protein subunit vaccine consisting of RSV sF + GLA-SE can induce robust neutralizing antibody and T cell responses to RSV, enhancing viral clearance via a TH1 immune-mediated mechanism. This vaccine may benefit older populations at risk for RSV disease.
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Stacie L
authors: SL
authors: Lambert
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Shahin
authors: S
authors: Aslam
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Elizabeth
authors: E
authors: Stillman
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Mia
authors: M
authors: MacPhail
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Christine
authors: C
authors: Nelson
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Bodrey
authors: B
authors: Ro
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Rosemary
authors: R
authors: Sweetwood
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Yuk Man
authors: YM
authors: Lei
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Jennifer C
authors: JC
authors: Woo
authors: Department of Research, MedImmune, Mountain View, California, United States of America.
authors: Roderick S
authors: RS
authors: Tang
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D002465:Cell Movement / Q000276:immunology; D003412:Cricetulus; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma