Introduction 127

Chapter 6: Vaccines

Stephen Korsman

Introduction

Vaccines are apathogenic entities that cause the immune system to respond in such a way, that when it encounters the specific pathogen represented by the vaccine, it is able to recognise it – and mount a protective immune response, even though the body may not have encountered that particular pathogen before.

Influenza viruses have been with mankind for at least 300 years, causing epidemics every few years and pandemics every few decades. They result in 250,000 – 500,000 deaths, and about 3-5 million cases of severe illness each year worldwide, with 5-15 % of the total population becoming infected (WHO 2003). Today, we have the capability to produce 300 million doses of trivalent vaccine per year – enough for current epidemics in the Western world, but insufficient for coping with a pandemic (Fedson 2005).

The influenza vaccine is effective in preventing disease and death, especially in high risk groups, and in the context of routine vaccination, the World Health Organization reports that the “influenza vaccine is the most effective preventive measure available” (WHO 2005e). With regard to the present fear of an imminent influenza pandemic, “Vaccination and the use of antiviral drugs are two of the most important response measures for reducing morbidity and mortality during a pandemic.” (WHO 2005d).

Vaccine Development

History

The concept of vaccination was practiced in ancient China, where pus from smallpox patients was inoculated onto healthy people in order to prevent naturally acquired smallpox. This concept was introduced into Europe in the early 18th century, and in 1796, Edward Jenner did his first human experiments using cowpox to vaccinate (vacca is Latin for cow) against smallpox. In 1931, viral growth in embryonated hens’ eggs was discovered, and in the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used in the Second World War (Baker 2002, Hilleman 2000). Greater advances were made in vaccinology and immunology, and vaccines became safer and mass-produced. Today, thanks to the advances of molecular technology, we are on the verge of making influenza vaccines through the genetic manipulation of influenza genes (Couch 1997, Hilleman 2002).

Yearly Vaccine Production

All vaccines in general use today are derived from viruses grown in hens’ eggs, and contain 15 µg of antigen from each of the three strains selected for that year’s vaccine – two influenza A strains (H1N1 and H3N2) and one influenza B strain. From

128 Vaccines

the selection of the strains to be used in the vaccine, all the way to the final vaccine, is a lengthy process that may take up to 6–8 months.

Selection of the yearly vaccine strain

Throughout the year, 110 national influenza surveillance centres and 4 WHO collaboration centres in 82 countries around the world watch the trends in circulating strains of influenza. Genetic data is collected, and mutations identified. The WHO identifies the strains that are likely to most resemble the strains in circulation during the next year’s winter seasons, and this information is shared with vaccine producers, who begin preparation for vaccine production.

This decision is made each year in February for the following northern hemisphere winter and September for the following southern hemisphere winter. Details of the planned February 2006 meeting can be seen on the WHO website (WHO 2005k).

For the northern hemisphere winter season from the end of 2004 to the beginning of 2005, the recommendations were as follows (WHO 2005h-i):

!an A/New Caledonia/20/99(H1N1)-like virus

!an A/Fujian/411/2002(H3N2)-like virus

!a B/Shanghai/361/2002-like virus

For the southern hemisphere winter season of mid-2005, the recommendations were:

!an A/New Caledonia/20/99(H1N1)-like virus

!an A/Wellington/1/2004(H3N2)-like virus

!a B/Shanghai/361/2002-like virus

For the northern hemisphere winter season of 2005-2006, the recommendations are:

!an A/New Caledonia/20/99(H1N1)-like virus

!an A/California/7/2004(H3N2)-like virus

!a B/Shanghai/361/2002-like virus

For the southern hemisphere winter season of mid-2005, the recommendations are:

!an A/New Caledonia/20/99(H1N1)-like virus

!an A/California/7/2004(H3N2)-like virus

!a B/Malaysia/2506/2004-like virus

For example, A/New Caledonia/20/99(H1N1) means that it is an influenza A, type H1N1, the 20th isolate from New Caledonia in 1999. One can see that the H1N1 influenza A in the vaccine still represents the circulating strain, while the H3N2 virus has changed over time. Obviously, A/Fujian/411/2002 was not a good prediction in 2004. As a matter of fact, the rate of vaccine failure was unusually high during the winter season 2004/2005.

Processes involved in vaccine manufacture

Shortly after the WHO announces the anticipated circulating strains for the coming season, vaccine manufacturers start making the new vaccine strain. If the strain