Elsevier

Vaccine

Volume 21, Issue 16, 1 May 2003, Pages 1776-1779
Vaccine

The annual production cycle for influenza vaccine

https://doi.org/10.1016/S0264-410X(03)00071-9Get rights and content

Abstract

Influenza disease impacts every year up to 10% of the world’s population, i.e. up to 500 millions of people. The international surveillance network organised by WHO allows the detection of important antigenic variation of the virus in humans but also animals (especially birds and pigs). Epidemiological data are summarised twice a year in two meetings (one in February, the other in September) allowing WHO to propose new recommendations for vaccines formulations for each northern and southern hemisphere influenza season annual vaccination. According to such recommendation, vaccine manufacturers proceed each year with two different vaccine production campaigns in order to match the vaccine composition with global epidemiological surveillance data and so, develop each time an updated vaccine formulation. To date within 6 months production periods, almost 250 million of doses are brought annually on market in more than 100 countries. In such a tight schedule, the annual production requires careful coordination of a highly complex process involving both public health laboratories and vaccine companies, in order to provide on time safe and effective vaccines. Major steps of this vaccine production process including the milestones and the bottlenecks need to be detailed in order to well understand difficulties and hurdles towards increase of global capacity and introduction of new vaccines.

Introduction

The acute respiratory illness known as influenza appears to have afflicted humans since ancient times. Hippocrates described an influenza-like epidemic in 412 BC and numerous similar episodes have been described since then. They were once widely believed to be the result of adverse astrological alignments or other occult influences. In 1933, a virus was identified as the causative agent by Smith et al. [1]. The first inactivated influenza vaccines were introduced in the 1940s. Since then, vaccine companies have developed expertise in a safe and effective vaccine manufacturing process, allowing production of an increasing number of doses of the influenza vaccine each year. This article briefly reviews this production process.

Section snippets

WHO epidemiological surveillance

The hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of influenza viruses change frequently as a result of genetic mutation. For this reason, the World Health Organization (WHO) coordinates an international surveillance system to monitor the epidemiology of influenza viruses [2]. This system, established in 1947, allows for the detailed analysis of circulating influenza viruses isolated from both humans and animals, especially birds and pigs, and is able to detect newly evolved

Vaccine manufacturing timetable

Once the virus strains to be included in next season’s vaccine have been determined, candidate high-growth seed strains must be prepared by the WHO Collaborating Centers, tested by the manufacturers and put into production. Several factors govern the vaccine production timetable. First, manufacturers must undertake two production cycles each year; one each for the Northern and Southern hemispheres. Second, timing the delivery of vaccine is crucial because annual vaccination programs are

Characterizing the strains used for vaccine production

Currently, two subtypes of influenza A virus (H3N2 and H1N1) and one strain of influenza B virus are responsible for outbreaks of human disease and are, therefore, included in influenza vaccines. During the period since influenza A (H3N2) viruses re-emerged in 1968, the A (H3N2) strains chosen for the vaccine have been changed twice as often as have the strains for the other two influenza viruses. During the 21-years period from 1980/1981 to 2001/2002, 14 strains changes were made in the

Conclusions

The production of influenza vaccines requires careful coordination of a highly complex process involving a wide range of technical expertise in both public health laboratories and vaccine companies in order to provide on time safe and effective vaccines. Its remarkable success is self-evident; within two 6-month production periods, almost 250 million doses are brought to market in more than 100 countries each year [8]. The process of producing influenza vaccine can be expected to become even

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