6 Challenges to vaccine development
6.1 Introduction
Vaccination seems such a straightforward and effective strategy for controlling infectious disease that the question arises of why we cannot develop vaccines against every pathogen and parasite.
Activity 21
Suggest reasons why effective vaccines already exist (a) against polio, but not against HIV infection; (b) against influenza, but not the common cold; and (c) against tetanus, but not syphilis.
Answer
(a) Polio virus is genetically fairly stable, so the organism does not mutate and there are only three strains to be included in the vaccine. In contrast, the surface molecules of HIV mutate so quickly that antigenic drift occurs continuously even within a single infected individual, making a vaccine extremely difficult to design. And we have yet to discover what would be an effective immune response against HIV.
(b) At any one time there are only a few strains of influenza virus in circulation, so although current vaccines only protect recipients against known strains, the emergence of vaccine-resistant virus is a relatively rare occurrence. Compare this with the viruses that causes colds, of which there are more than 100 in circulation. Moreover influenza is a much more serious illness than the common cold, so there is much more incentive to develop a vaccine against it.
(c) Tetanus presents a well-defined target for the immune response, since we know that antibodies against the toxoid will neutralise it; in contrast we are mostly ignorant of what constitutes an effective immune response against the spirochaetes that cause syphilis.
Comparisons such as these reveal that the factors limiting vaccination strategies to control infectious diseases fall into five broad categories.
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The nature of the pathogen: including, its distribution in human populations and whether it infects non-human hosts; its mode and speed of transmission; the type of symptoms it causes; whether the disease has a symptom-free latent period or a ‘carrier’ state.
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The nature of the immune response: including, whether antibody-mediated or cell-mediated immunity predominates in an effective immune response; the type and location of protective responses; the identification and immunogenicity of critical antigens; scientific knowledge of how to enhance the immune response.
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Economic factors: including, whether it is cost-effective to develop a vaccine and whether a vaccine would be affordable by those who would benefit most from it.
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Organisational factors: including, whether the infrastructure and personnel necessary to conduct a vaccination programme exist in a susceptible population.
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Cultural factors: including, the level of public understanding of what vaccination can (and cannot) protect against, and concerns about vaccine safety.
These categories cannot be considered in isolation from each other: the co-evolution of pathogens and their hosts means that (1) and (2) above are intrinsically related and continuously changing; the state of scientific knowledge of the pathogen and host immune responses influence whether (3) the economic case will favour research into a new vaccine; an effective vaccine may be produced, but organisational difficulties (4) may mean that it cannot be delivered where it is most needed (e.g. due to lack of refrigerated storage facilities or trained vaccinators); and (5) concerns about safety may limit vaccine uptake.
In the rest of this section, we consider biological factors of the pathogen and the host, which present challenges to the development of vaccines. In Section 7, we turn to the economic, organisational and cultural limitations on vaccination as a strategy to control infectious disease.