Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
The practice of vaccination began, based on empirical observations, about 200 years ago.
Edward Jenner first observed that milkmaids showing symptoms of cowpox appeared to be
less susceptible to later infection by smallpox, suggesting that they were protected from
smallpox by previous exposure to a similar disease. It was only at the end of the 19 th century
that the rationale behind vaccination was first appreciated, with the discovery that immune
serum contains molecules that can neutralize toxins or bacteria. Methods to inactivate whole
bacteria and passage of pathogens in alternative animal hosts, resulting in the selection of less
virulent strains were used to develop vaccines against various agents, such as typhoid, cholera
and tuberculosis. In the 20 th century, new techniques of virus growth in cell culture and
genetic engineering allowed for the development of new vaccines (Plotkin and Plotkin, 2011).
It became clear that, in many cases, the presence of neutralizing antibodies correlated with the
observed protection against the pathogen. The aim then became to render the infectious agents
less virulent but still immunogenic. While the presence of antibodies was considered to be the
most important characteristic of protection, two vaccines (the Bacille Calmette-Guérin- BCG,
and the varicella zoster virus vaccine) were shown to be dependent on T cell immunity.
Indeed, while most of the successful vaccines developed thus far are based on the generation
of protective antibodies, it is also crucial to develop vaccines capable of eliciting protective T-
cell responses. Vaccines that have been developed successfully have the advantage that they
target agents that have limited antigen diversity and thus, can be treated by antibodies (Figure
1). However, there remain many diseases for which efficient vaccines are not yet available
because of extensive antigen variability and/or the requirement for T cell immunity (Rappuoli
and Aderem, 2011). Viruses like HIV that evolve and mutate quickly, or parasites such as
Plasmodium that are found in different forms display a variety of antigenic compositions that
change frequently. Consequently, neutralizing antibodies are not efficient to mediate potent
protection against these pathogens. Moreover, T cell immunity has been shown to be crucial
to controlling HIV and Mycobacterium tuberculosis infection. New approaches are thus
required to develop vaccines that target these difficult-to-control pathogens.
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