Developing Vaccines to Combat Pandemic Influenza

James S Robertson,Othmar G Engelhardt

doi:10.3390/v2020532

Abstract

Influenza vaccine manufacturers require antigenically relevant vaccine viruses that have good manufacturing properties and are safe to use. In developing pandemic vaccine viruses, reverse genetics has been employed as a rational approach that can also be used effectively to attenuate the highly virulent H5N1 virus and at the same time place the H5 HA and N1 NA on a background of PR8, a virus that has been used over many decades to provide high yielding vaccine viruses. Reverse genetics has also been used successfully alongside classical reassorting techniques in the development of (swine flu) pandemic A(H1N1)v vaccine viruses.

Highlights

Influenza vaccines were first developed over 60 years ago [1]
The scope of this review is to describe the development of the viruses that are required by the vaccine industry in order for them to manufacture an egg-derived inactivated vaccine
Studies have shown that at minimum, high growth reassortants (HGR) based upon PR8 had the PR8 segment encoding the matrix protein [11]. Whilst this process of deriving an HGR remains an essential element of influenza vaccine production, it is highly serendipitous and successful derivation of a useful HGR

Summary

Introduction

Influenza vaccines were first developed over 60 years ago [1]. They were based upon growth of virus in embryonated hens’ eggs and inactivation of the virus. The scope of this review is to describe the development of the viruses that are required by the vaccine industry in order for them to manufacture an egg-derived inactivated vaccine. The intent was that such recombinant viruses would be useful for the efficient manufacture of influenza vaccine This was the case and vaccine derived from a genetically recombined virus was shown to have the appropriate immunogenicity in humans [8]. Studies have shown that at minimum, high growth reassortants (HGR) based upon PR8 had the PR8 segment encoding the matrix protein [11] Whilst this process of deriving an HGR remains an essential element of influenza vaccine production, it is highly serendipitous and successful derivation of a useful HGR within the short time frame of the annual influenza vaccine manufacturing season is not guaranteed

Reverse Genetics

Use of Reverse Genetics to Derive Safe H5N1 Candidate Vaccine Viruses

Library of Viruses of Pandemic Potential

22 July 09