Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

Lemaire, D.; Barbosa, T.; Rihet, P.

It is very likely that populations with different genetic backgrounds will differ in their genetic control of infectious diseases: for a particular infectious disease, the involvement of some loci may be evidenced in a population living in Africa and may not be detected in another one living in Asia. Ethnic groups living in the same area can also differ in their ability to control infection or disease. For example, the Fulani, whose genetic background is clearly different from that of other ethnic groups in West Africa, have been compared to sympatric ethnic groups for several phenotypes related to malaria resistance. The Fulani produce higher antibody levels than the Mossi and the Rimaibe, and have lower parasite densities and fewer and milder malaria attacks, indicating that the Fulani are more resistant against malaria than the Mossi and the Rimaibe (50) . Similarly, it is known that populations differ in their response to vaccination, suggesting that populations differ in the frequency of the protective alleles. Poland et al. (51) have reported that native (Innu and Inuit) and Caucasian schoolchildren differed in their production of antibodies against measles antigens after vaccination in Canada. Additionally, Malawi and UK populations strikingly differed in the level of prowww.bjournal.com.br Braz J Med Biol Res 45 (5) 2012 tection following BCG vaccination (i.e., 0% in Malawi and 80% in the UK), and in their IFN-γ production in response to mycobacterium antigens (52) . Furthermore, native children (Navajo, White Mountain Apache and Alaska) and children in the general US population differed in the incidence of disease due to H. influenzae type b both before and after vaccination, indicating that native children were more susceptible than other children in the US, and that their response to vaccination was also weaker (53) . Further understanding of the genetic basis of variation in vaccine response may lead investigators to consider different vaccine strategies for groups having different genetic backgrounds. The combination of high throughput methodologies and multifactorial analyses may help in the identification of genetic markers that affect immune and physiological responses leading to serious adverse effects, thus allowing the identification of groups at risk of vaccine-induced adverse events, which would be entitled to preventive therapies or alternative vaccine formulations (54) . In the same way, the exposure to the infectious agents, current immune status (e.g., immunocompromised subjects), gender, and age could be taken into account to minimize the rate of vaccine failure or vaccine adverse events. Such a targeted-group vaccination approach requires more information about the human groups of interest. Efforts are particularly needed to study various populations in Africa, where genetic diversity is the most important in the world, and data are lacking. In these populations, the international scientific and medical community would be able to screen for millions of polymorphisms within each potential target group.