Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

For instance, a study in The Gambia with 48 monozygous and 159 dizygous infant twin pairs living together looked into environmental vs. genetic regulation of immune response to BCG, oral polio, HepB, diphtheria, pertussis, tetanus at 5 months. All antibody responses were heritable, particularly in the case of HepB and polio vaccines, and genetic factors, specially non-HLA genes play important role modulating vaccine response in infants. 104 Another twin study analysed 78 monozygous and 27 dizygous healthy pairs (8-82 years old) for 204 different immune parameters comprising cell population frequencies, cytokine responses and serum proteins. Both innate and adaptive cell population frequencies were influenced mostly by non-heritable parameters (61% of all populations) but others were under very strong influence of heritable factors. The article also reports that the 51 serum proteins measured showed great variation in heritability. In addition the authors looked at variation in heritability of traits between young and older MZ twin cohorts (<20, 13 median and >60, 72 median years old, respectively) and noted that in several cases, there was a decrease in correlation with age, likely reflecting different environmental exposures and possibly also epigenetic changes. Further, analysis of antibody responses to seasonal influenza vaccine (2009, 2010, 2011) indicates influence from mostly non-heritable components. Overall, heritability of immune traits tends to decrease with age, likely reflecting the effect of exposure to environment. 105 These and other studies indicate genetic influences to immune responses associated with both coding and non-coding regions of the genome and that are under strong influence of environmental factors. [106] [107] [108] [109] Querec et al. 110 also used systems vaccinology methods to identify markers that predict responses to yellow fever vaccine YF-17D. They evaluated 15 healthy volunteers (in 1 st year) and 10 (in 2 nd year) at days 0, 1, 3, 7, 21 and noted that 65 genes such as CXCL10 and IL-1α were modulated in both trials (associated with immunological responses and cell motility). Peak gene expression were observed at 7 days, with the largest category involved in antiviral and interferon responses. Interestingly, transcript levels of TNFRSF17/BLys-BAFF at day 7 were predictive of antibody responses for both trials. 110 Another example of systems vaccinology came from the analysis of signatures for live attenuated (LAIV, n = 28) and trivalent inactivated influenza vaccines (TIV, n = 28). Data showed poor responses for LAIV at day 28. CXCL10 was induced in plasma samples from TIV and microarray data from PBMCs of the 56 individuals at days 0, 3, 7 shows 1,445 genes differentially modulated in both vaccines (including common inflammatory and antimicrobial genes for TIV, LAIV, and also interferon genes modulated for LAIV, likely due to virus replication). Overall, there were distinct signatures for LAIV and TIV with the latter vaccine also showing upregulation of TNFRSF17. Antibody responses were predicted by kinase CaMKIV which is involved in T cell development, inflammatory response and maintenance of hematopoietic stem cells. At day 3, this parameter negatively correlates with antibody response on day 28 and immunizing KO CaMKIV and control WT mice with TIV led to 3 to 6.5-fold higher response on day 7 for KO. 111 Similar systems vaccinology analyses were published by Tsang et al. 112 for influenza vaccine