Improving pandemic H5N1 influenza vaccines by combining different vaccine platforms

Abstract

A variety of platforms are being explored for the development of vaccines for pandemic influenza. Observations that traditional inactivated subvirion vaccines and live-attenuated vaccines against H5 and some H7 influenza viruses were poorly immunogenic spurred efforts to evaluate new approaches, including whole virus vaccines, higher doses of antigen, addition of adjuvants and combinations of different vaccine modalities in heterologous prime–boost regimens to potentiate immune responses. Results from clinical trials of prime–boost regimens have been very promising. Further studies are needed to determine optimal combinations of platforms, intervals between doses of vaccines and the logistics of deployment in pre-pandemic and early pandemic settings.

Keywords::

• influenza vaccine
• pandemic influenza vaccine
• prime boost

Financial & competing interests disclosure

This research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. CJ Luke is a member of the Executive Committee for a Cooperative Research and Development Agreement between NIH and MedImmune. K Subbarao is Principal Investigator on a Cooperative Research and Development Agreement between NIH and MedImmune for the development of live-attenuated pandemic influenza vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• In recent years, there has been an explosion in the field of vaccine development for influenza, including efforts to develop practical and effective pandemic influenza vaccines, and universal influenza vaccines.

• Inactivated vaccines against potential pandemic strains of avian influenza are uniformly suboptimal in immunogenicity in humans.

• Several vaccination regimens that include a heterologous priming modality followed by inactivated vaccine boost show promise in early clinical trials in humans.

• Different combinations of prime and boost vaccine platforms should be compared for their ability to enhance immunogenicity of pandemic influenza vaccines.

• Clinical and nonclinical studies should be conducted to determine the optimal interval between different vaccine modalities and the importance of the order in which the vaccines are administered. Such studies will be of great value in informing pandemic vaccine policy.