title: An Intranasal Proteosome-Adjuvanted Trivalent Influenza Vaccine Is Safe, Immunogenic & Efficacious in the Human Viral Influenza Challenge Model. Serum IgG & Mucosal IgA Are Important Correlates of Protection against Illness Associated with Infection.
abstract: BACKGROUND
  A Proteosome-adjuvanted trivalent inactivated influenza vaccine (P-TIV) administered intra-nasally was shown to be safe, well tolerated and immunogenic in both systemic and mucosal compartments, and effective at preventing illness associated with evidence of influenza infection.
  
  
  METHODS
  In two separate studies using the human viral challenge model, subjects were selected to be immunologically naive to A/Panama/2007/1999 (H3N2) virus and then dosed via nasal spray with one of three regimens of P-TIV or placebo. One or two doses, 15 μg or 30 μg, were given either once only or twice 14 days apart (1 x 30 μg, 2 x 30 μg, 2 x 15 μg) and subjects were challenged with A/Panama/2007/1999 (H3N2) virus. Immune responses to the vaccine antigens were measured by haemagglutination inhibition assay (HAI) and nasal wash secretory IgA (sIgA) antibodies.
  
  
  RESULTS
  Vaccine reactogenicity was mild, predictable and generally consistent with earlier Phase I studies with this vaccine. Seroconversion to A/Panama/2007/1999 (H3N2), following vaccination but prior to challenge, occurred in 57% to 77% of subjects in active dosing groups and 2% of placebo subjects. The greatest relative rise in sIgA, following vaccination but prior to challenge, was observed in groups that received 2 doses.
  
  
  CONCLUSIONS
  Intranasal vaccination significantly protected against influenza (as defined by influenza symptoms combined with A/Panama seroconversion) following challenge with A/Panama/2007/1999 (H3N2). When data were pooled from both studies, efficacy ranged from 58% to 82% in active dosing groups for any influenza symptoms with seroconversion, 67% to 85% for systemic or lower respiratory illness and seroconversion, and 65% to 100% for febrile illness and seroconversion. The two dose regimen was found to be superior to the single dose regimen. In this study, protection against illness associated with evidence of influenza infection (evidence determined by seroconversion) following challenge with virus, significantly correlated with pre-challenge HAI titres (p = 0.0003) and mucosal sIgA (p≤0.0001) individually, and HAI (p = 0.028) and sIgA (p = 0.0014) together. HAI and sIgA levels were inversely related to rates of illness.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02522754.
authors.affiliation: hVIVO Group PLC., Queen Mary BioEnterprises Innovation Centre, London, United Kingdom.
authors.forename: Rob
authors.identifier: http://orcid.org/0000-0003-2107-0174
authors.initials: R
authors.lastname: Lambkin-Williams
authors.affiliation: University Hospitals Coventry & Warwickshire NHS|| Trust, Clifford Bridge Road, Walsgrave, Coventry, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Gelder
authors.affiliation: ID Biomedical Corporation of Québec, 7150 Frederick Banting, Saint-Laurent, Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Broughton
authors.affiliation: ID Biomedical Corporation of Québec, 7150 Frederick Banting, Saint-Laurent, Québec, Canada.
authors.forename: Corey P
authors.initials: CP
authors.lastname: Mallett
authors.affiliation: hVIVO Group PLC., Queen Mary BioEnterprises Innovation Centre, London, United Kingdom.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Gilbert
authors.affiliation: hVIVO Group PLC., Queen Mary BioEnterprises Innovation Centre, London, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Mann
authors.affiliation: Analytical Solutions Group, Inc., 14730 Soft Wind Drive, North Potomac, MD, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: He
authors.affiliation: Queen Mary's School of Medicine and Dentistry, London, United Kingdom.
authors.forename: John S
authors.initials: JS
authors.lastname: Oxford
authors.affiliation: ID Biomedical Corporation of Québec, 7150 Frederick Banting, Saint-Laurent, Québec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Burt
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000032:analysis*; D007074:Immunoglobulin G / Q000097:blood*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D015990:Placebo Effect; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated