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

• Published in: PloS one 2015-03, Vol.10 (3), p.e0119509-e0119509
• Main Authors: Lambert, Stacie L, Aslam, Shahin, Stillman, Elizabeth, MacPhail, Mia, Nelson, Christine, Ro, Bodrey, Sweetwood, Rosemary, Lei, Yuk Man, Woo, Jennifer C, Tang, Roderick S
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic; Adults; Age; Alum; Aluminum sulfate; Animal models; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Movement - immunology; Cell-mediated immunity; CHO Cells; Cotton; Cricetulus; Cytokines; Disease; Disease Models, Animal; Female; Formulations; Glycoproteins; Health risks; Humoral immunity; Immune clearance; Immunity; Immunity, Cellular; Immunity, Humoral; Immunization; Immunogenicity; Immunoglobulin G; Immunoglobulins; Infants; Infections; Influenza; Interferon-gamma - metabolism; Lipid A; Lipids; Lung - immunology; Lung - pathology; Lung - virology; Lungs; Lymphocytes; Lymphocytes T; Mice; Neutralizing; Older people; Proteins; Rats; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Viruses - immunology; Robustness; Rodents; T cell receptors; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; TLR4 protein; Toll-like receptors; Traffic models; Vaccines; Vaccines, Subunit - immunology; Viral infections; Viruses; Young adults; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119509

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. 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. 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.