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

Abstract

Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.

Plasmodium falciparum pre-erythrocytic stage vaccine development

“…They can be boosted when co-administered with adjuvants, thereby overcoming problems such as reverse virulence and the difficulty of obtaining sufficient amounts of the antigen to facilitate large-scale production [45]. However, using unsuitable antigens having low immunogenicity and a high genetic variation rate has limited the emergence of efficient vaccines against diseases such as malaria [46]. One of the main antigens involved in this approach has been P. falciparum CSP [11] used as a subunit in the RTS,S vaccine.…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…The advent of the genome era and the tremendous advances in immunological and bioinformatics tools have enabled the reverse vaccinology approach (RV) as a new effective strategy for lead antigen identification in vaccine development ( 73 – 75 ). One of the advantages of the RV approach is that every antigen encoded in the worm genome can be screened in silico to determine its ability to induce an immune response ( 31 , 74 ).…”

New vaccines on the horizon

“…Prema tome, jedan od glavnih izazova u razvoju novih strategija imunizacije je dizajniranje vakcina koje će stimulisati odgovarajući tip imunskog odgovora koji može da obezbedi imunost uglavnom na intraćelijske patogene, naročito na one koji dovode do razvoja hroničnih, često doživotnih infekcija. Poznavanje biologije visoko konzerviranih antigena koji su uključeni u patogenezu bolesti, kao i imunskih mehanizama koje treba stimulisati da bi se indukovala zaštita, je neophodno za racionalno osmišljavanje vakcinalnih strategija kojima bi se mogao obezbediti bolji protektivni imunitet u odnosu na onaj koji se prirodno indukuje (27).…”