For instance, subjects classified as non-responders to Haemophilus influenzae type b polysaccharide vaccine–based on their GM 23 and KM 1 allotype status–became responders when the vaccine was conjugated to a suitable adjuvant [40-42]. determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to P. vivax apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses. Results IgG1 antibody levels to Ivacaftor hydrate both PvMSP1-19 and PvAMA-1 antigens were significantly higher (P = 0.004, P = 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype. Conclusions Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to P. vivax malaria antigens. These findings have important implications for the effectiveness of vaccines made up of PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci. Background Malaria is present in nearly 90 countries with approximately 2.5 billion people exposed to infection by Plasmodium falciparum and Plasmodium vivax [1]. Although causing less mortality than P. falciparum, P. vivax contamination has an enormous socioeconomic impact. P. vivax is usually a widely distributed human malarial parasite, prevalent in South America, Asia and Oceania, and the 70-80 million cases currently recorded annually are of global public health importance [2]. Plasmodium vivax is usually now recognized as a cause of severe and fatal malaria, despite its low parasitaemia, the increased deformability of vivax-infected red blood cells and an apparent paucity of parasite sequestration [3]. The most cost-effective measure to control infectious diseases like malaria is a vaccine and effective malaria vaccines are still not available. Antigens of Plasmodium located on the surface or in the apical organelles of merozoites have been characterized as targets for protection or Ivacaftor hydrate as possible vaccine antigens against malaria [4]. Among them, the apical membrane antigen 1 (AMA-1) and a 19-kDa fragment of merozoite surface protein-1 (MSP1-19) are the FLJ12455 leading candidates for inclusion in a vaccine against blood stages of malaria. AMA-1 is an 83-kDa antigen synthesized during the mature stages of the parasite; it is thought to be involved in the process of erythrocyte invasion [4]. MSP1-19 is usually a portion of MSP1 produced after two processing steps and remains attached to the newly formed ring stage parasite after invasion [5]. Active immunization of experimental animals with either native or recombinant forms of both proteins has been shown to be protective against challenge infection [6]. Moreover, antibodies to MSP1-19 and AMA-1 inhibited invasion of red blood cells [7]. Humoral immune responses, which have a substantial genetic component [8], play a key role in the development of immunity to malaria. Identification and understanding of the mechanisms of action of host genetic factors that contribute to the naturally occurring anti-malarial immune responses is of utmost importance. The current paucity of knowledge in this area hinders effective Ivacaftor hydrate immunological intervention and confounds the evaluation of ongoing vaccine efficacy trials. The few immune response genes identified thus far do not account for the total inter-individual variability in antibody responsiveness to malarial antigens [9,10], implying the involvement of additional genes. Immunoglobulin (Ig) allotypes are important candidates for controlling immune responsiveness, as evidenced by their association with humoral immunity to a variety of pathogens [11-16]. The role these polymorphic determinants play in Ivacaftor hydrate antibody responses to malarial antigens, however, is not fully understood. There are striking Ivacaftor hydrate qualitative and quantitative differences in the distribution of Ig GM and KM allotypes among different ethnic groups [17,18]. Additionally, there is almost complete linkage disequilibrium between particular GM determinants within an ethnic group, and every major group is.