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

Vaccine. 2014 Jul 31;32(35):4592-4597. doi: 10.1016/j.vaccine.2014.05.039. Epub 2014 May 21.


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.

Keywords: Cell culture; Clinical trial; H1N1; Influenza; Pandemic; Vaccine.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Aged
  • Aluminum Hydroxide / administration & dosage
  • Antibodies, Viral / blood
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / isolation & purification
  • Influenza, Human / epidemiology
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Pandemics / prevention & control*
  • Placebos / administration & dosage
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / isolation & purification
  • Young Adult


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines
  • Placebos
  • Vaccines, Synthetic
  • Aluminum Hydroxide

Associated data

  • CTRI/CTRI/2010/091/000152
  • CTRI/CTRI/2010/091/000661