Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults

ABSTRACT

This study was a phase I double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a Serbian-produced seasonal trivalent split, inactivated influenza vaccine in healthy adults. The vaccine was manufactured in eggs by the Torlak Institute of Virology, Vaccines and Sera, Belgrade, Serbia and contained A/H1N1, A/H3N2 and B viruses. The clinical trial took place at the Clinical Center of Serbia in Belgrade. Sixty healthy volunteers, aged 18–45 years, were enrolled in the trial. On the day of immunization, volunteers were randomly assigned to receive either a single dose of the trivalent seasonal influenza vaccine (15 μg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Subjects were monitored for adverse events through a clinical history and physical examination, and blood was taken for testing at screening and on day 8 to assess vaccine safety. Serum samples obtained before and 21 days after immunization were tested for influenza antibody titers using hemagglutination-inhibition (HAI) and microneutralization (MN) tests. No serious adverse events were reported. Pain and tenderness at the injection site were the most commonly reported symptoms in both vaccine and placebo groups. Overall, serum HAI responses of fourfold or greater magnitude were observed to H1, H3, and B antigen in 80%, 75%, and 70% of subjects, respectively. Seroprotection rates as measured by HAI were also high (100%, 100% and 86.67%, respectively, for H1, H3 and B). Thus, Torlak's seasonal trivalent influenza vaccine was not associated with adverse events, was well-tolerated and immunogenic. It should be further evaluated in clinical trials to provide sufficient safety and immunogenicity data for licensing in Serbia.

KEYWORDS:

• Seasonal influenza vaccine
• trivalent inactivated split
• clinical trial
• Serbia
• Torlak

Disclosure of potential conflicts of interest

Authors declare that there is no conflict of interest. ClinicalTrials.gov identifier: NCT02585700, October 13, 2015

Acknowledgments

We thank John Donnelly for his dedication to this program, David Taylor, Joseph Chiu and Iksung Cho for their work on protocol development, and Niraj Rathi for coordinating the development of this manuscript. We thank Zorica Nikolic and Vesna Obradovic of the Clinical Center of Serbia for their support as nurses during the trial. We also thank Comac Medical for providing the clinical monitoring, data management and analysis services.

For their support towards the project to establish influenza vaccine production in Serbia we thank Florence Barthelemy, Martin Friede, Miljana Grbic and Marie-Paule Kieny at the World Health Organization as well as Rick Bright, Sheng Li, Chuong Huynh and Julie Schafer at the Biomedical Advanced Research and Development Authority (BARDA), US Department of Health and Human Services.

Additional information

Funding

Financial support for the study was provided to WHO and to PATH from the US Department of Health and Human Services/BARDA (Grant Numbers: IDSEP130015-01 and IDSEP130018-01-06).