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

• Published in: Vaccine Vol. 32; no. 35; pp. 4592 - 4597
• Main Authors: Basavaraj, V.H., Sampath, G., Hegde, Nagendra R., Mohan, V. Krishna, Ella, Krishna M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 31.07.2014; Elsevier; Elsevier Limited
• Subjects: Adjuvants, Immunologic - administration & dosage; Adolescent; Adult; Adults; adverse effects; Aged; Allergy and Immunology; Alum; Aluminum; aluminum hydroxide; Aluminum Hydroxide - administration & dosage; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; Cell culture; Clinical trial; Clinical trials; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Fever; Fundamental and applied biological sciences. Psychology; H1N1; hemagglutinins; Humans; immune response; Immunization; Immunogenicity; Influenza; 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; Injection; injection site; Male; Microbiology; Middle Aged; Miscellaneous; Pain; Pandemic; Pandemics; Pandemics - prevention & control; Pharmaceutical industry; Placebos - administration & dosage; Seroconversion; Side effects; Src protein; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Vaccines, Synthetic - isolation & purification; Virology; Young Adult; India; Cell culture; Pandemic; Clinical trial; Vaccine; H1N1; Influenza; HIN1; Orthomyxoviridae; Infection; Virus; Influenzavirus A; Immunogenicity; Influenza A virus; Viral disease
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2014.05.039

•Clinical trials of a cell-based influenza vaccine from India is reported.•The vaccine was well tolerated in Phase I and Phase II/III trials.•A single dose of the vaccine was immunogenic.•The vaccine met the licensing criteria. 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 15μg 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.