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
| Autor: | Jennifer Woo, Mia MacPhail, Rosemary Sweetwood, Christine Nelson, Bodrey Ro, Shahin Aslam, Stacie L. Lambert, Yuk Man Lei, Elizabeth Ann Stillman, Roderick Tang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cellular immunity viruses lcsh:Medicine CHO Cells Respiratory Syncytial Virus Infections Biology CD8-Positive T-Lymphocytes medicine.disease_cause Antibodies Viral Virus Interferon-gamma Mice Immune system Cricetulus Th2 Cells Adjuvants Immunologic Immunity Cell Movement medicine Respiratory Syncytial Virus Vaccines Animals lcsh:Science Lung Immunity Cellular Multidisciplinary Viral Vaccine lcsh:R virus diseases respiratory system Th1 Cells Virology Antibodies Neutralizing Immunity Humoral Rats Respiratory Syncytial Viruses Disease Models Animal Respiratory syncytial virus (RSV) Immunology Vaccines Subunit biology.protein lcsh:Q Female Immunization Antibody Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0119509 (2015) |
| ISSN: | 1932-6203 |
| Popis: | 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. Methodology and Principal Findings 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/Significance 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|