Development of measles vaccines

 

http://www.worldwidevaccines.com/public/diseas/mmr6.asp

The first attempts to prevent measles through vaccination were made in the
mid-18th century when a Scottish physician, Francis Home, inoculated 12
children with material from the blood of a measles patient. 10 of the
children developed a mild measles infection. The technique, known as
morbillisation, was never widely adopted.

However, it was not until 200 years later, in 1954, that the measles virus
was isolated and cultured in the USA.[37] This was a significant discovery
because it enabled inactivated vaccines and live-attenuated vaccines to be
produced. The use of killed, inactivated vaccines, however, was abandoned
in 1967 when it was established that they did not provide complete
protection and that some vaccinees suffered from unusual rashes when
exposed to live measles virus. Work on developing live-attenuated measles
vaccines continued, however.

In 1963, 9 years after the isolation of the measles virus, Enders and
colleagues used a strain of the natural virus derived from a patient called
Edmonston to make the live-attenuated Edmonston B measles vaccine. This was
obtained by passage of the Edmonston strain at 35-36°C 24 times in primary
kidney cells and 28 times in primary human amnion cells, adapting it to
chick embryos and further passaging in chick embryo cells. The vaccine was
immunogenic and protective and was licensed for use in the US in 1963.
Unfortunately, it produced a number of adverse reactions including fever,
rash, upper respiratory symptoms and occasionally convulsions. The
incidence of reactions to vaccination could be halved by the simultaneous
administration of gammaglobulins but many authorities considered that
adverse effects of the vaccine were too frequent and severe to justify its
widespread use.

In the search for better live measles vaccines to replace the Edmonston B
vaccine, further attenuation of the Edmonston strain was carried out by
several workers.

The Schwarz strain was obtained by passage of the Edmonston B strain a
further 85 times at 32°C in chick embryo cells. A vaccine containing this
strain was launched in the US in 1965 and was the first measles vaccine
with an acceptable reactogenicity profile.

The Moraten strain was obtained by passaging the Edmonston B virus at 32°C
an additional 40 times. A vaccine based on this strain was launched in 1968.

Both these vaccines are immunogenic and have a good reactogenicity profile.
They are therefore suitable for use without the need for gammaglobulins to
be given at the same time.

A major advance in the technology of measles vaccines came in 1975 with the
launch of a vaccine containing the Schwarz strain of measles virus by
SmithKline Biologicals. It was the first heat-stable measles vaccine
suitable for use in tropical countries and was therefore able to make a
significant contribution to vaccination campaigns in developing countries.

Other currently available live-attenuated vaccines based on the further
passaged Edmonston B strain include those which use the Edmonston-Zagreb
virus (which has undergone further passages in WI-38 human diploid cells)
and the AIK-C virus (which has been passaged in human amnion cells, sheep
kidney cells and chick embryo fibroblasts).

There are also some measles vaccines which are not derived from the
Edmonston virus. Vaccines derived from the Leningrad, Shanghai and Tanabe
measles strains are in use in eastern Europe, China and Japan respectively.

 
Figure 9 - Origin and passage history of some measles vaccine strains.
(Adapted from Hirayama M. Measles vaccines used in Japan. Rev. Infect. Dis.
1983 ; 5(3) : 495-503)

The efficacy of current measles vaccines ranges from 90 to 95%[38] and
immunity following measles vaccination has been shown to last for longer
than 20 years and is probably lifelong.[1, 39] [Figure 9]

--------------------------------------------------------
Sheri Nakken, R.N., MA
moderator
Vaccination Information & Choice Network, Nevada City CA & UK
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