Genetic Markers of Immune Response to Yersinia pestis F1 and V Antigens-loaded Microspheres Vaccine Against Plague

Abstract

An efficient immune response to a vaccine depends on activation of antigen-presenting cells and antigen-specific T and B lymphocytes, induction of memory cells, regulatory cells and antibody-secreting plasma cells, as well as on the persistence of the antigen in the body. The strength of immune response largely depends on the genes participating in this process. This study was focused on the gene polymorphism that could be responsible for insufficient immune response to a plague vaccine (molecular microencapsulated plague vaccine, MMPV) in a proportion of humans. After two subsequent vaccinations of the nine human volunteers, 67 % of them developed specific antibody titers equal to or exceeding the threshold level. However, 33 % of the subjects did not develop specific antibodies to either V, or F1 (Caf1) antigen during 90 days of observation post vaccination. We have investigated 20 single nucleotide polymorphisms (SNP) in 14 of immune response genes in an attempt to find an association between a particular allele and the ability to develop antibodies to MMPV antigens. Homozygosity for the IL1β gene wild type allele variant C-3953, or homozygosity for a mutated allele T-3953 allowed to produce anti-F1 IgG, whereas heterozygotes remained seronegative. Heterozygotes for the TLR9 gene at position 2848 (A2848G) were also responders to F1. Among responders to the V (LcrV) antigen, IgG production was observed only in carriers of mutant IL4 allele C-589T and in carriers of mutant allele of IL6 gene C-174G, either homozygotes or heterozygotes, and was not observed in homozygotes of the wild type allele. The lack of a mutant allele of IL10 gene C-819T was also associated with a non-responder phenotype. Our data suggest that potential non-responders to the MMPV may be identified by SNP in the IL1β (С-3953 Т), IL4 (C-589T), IL6 (С-174G), IL10 (C-819T), and TLR9 (A2848G) genes. Individuals with non-responder genotype should be included in the clinical trials assessing novel, universally effective plague vaccines.