title: Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies.
abstract: The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC in adults aged 18-65 years is reported. In the Phase I randomized, double-blind, placebo-controlled, single-centre study, 160 subjects were parallelly assigned 3:1 to vaccine:placebo groups (n=60:20) with both the aluminium hydroxide adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the formulations containing 15 μg of haemagglutinin protein showed minimal adverse reactions, the most common of which were pain at injection site (11.67%) and fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of ≥40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0 and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium hydroxide did not have a significant effect either on immunogenicity or on reactogenicity. Nevertheless, based on its recognized positive effects on the stability and immunogenicity of many vaccines, and its marginal benefit in both pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further tested in a staggered Phase II/III randomized, double-blind, placebo-controlled, multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1 to adjuvanted vaccine and placebo groups. In these studies, the most common adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT, meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and immunogenic to adults of 18-65 years.
authors.affiliation: Vydehi Institute of Medical Sciences and Research Centre, EPIP Area, White Field, Bengaluru 560066, India.
authors.forename: V H
authors.initials: VH
authors.lastname: Basavaraj
authors.affiliation: Institute of Preventive Medicine, Narayanaguda, Hyderabad 500029, India.
authors.forename: G
authors.initials: G
authors.lastname: Sampath
authors.affiliation: Ella Foundation, Genome Valley, Turkapally, Shameerpet Mandal, Hyderabad 500078, India. Electronic address: hegden@ellafoundation.org.
authors.forename: Nagendra R
authors.initials: NR
authors.lastname: Hegde
authors.affiliation: Bharat Biotech International Limited, Genome Valley, Turkapally, Shameerpet Mandal, Hyderabad 500078, India.
authors.forename: V Krishna
authors.initials: VK
authors.lastname: Mohan
authors.affiliation: Bharat Biotech International Limited, Genome Valley, Turkapally, Shameerpet Mandal, Hyderabad 500078, India.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Ella
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D058873:Pandemics / Q000517:prevention & control*; D010919:Placebos / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010919:Placebos; D014614:Vaccines, Synthetic; D000536:Aluminum Hydroxide
keywords: Cell culture; Clinical trial; H1N1; Influenza; Pandemic; Vaccine