Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

EE is a subclinical condition frequently encountered in lower income nations and that can be attributed to a combination of factors, including repeated exposure to oral-faecal contamination, inadequate nutrition and poor overall sanitation. Ultimately EE may lead to small intestinal bacterial overgrowth and gut microbiome imbalances. EE also correlates with stunting of affected individuals, and a variety of other symptoms such as decrease in intestinal barrier function, reduced nutrient absorption capacity and increased gut permeability, which facilitates crossing of pathogens and subsequent activation of the immune system. It is likely that chronic gut inflammation contributes to growth abnormalities and stunting. Also, there are major histological modifications in the small intestine including shortening of villi. [1] [2] [3] Such changes may be reversed over time with improved nutrition and sanitary conditions 4 and lead to a lower nutrient absorption surface, which in itself reduces the benefit of interventions including supplements and vaccines. A critical time for EE onset is the transition from breastfeeding to complementary feeding as the risk for oral-faecal contamination is greatly augmented. The negative impact of EE can be mitigated with varying degrees of success with improved hygiene, nutritional supplements such as zinc and other micronutrients, omega-3-rich lipids, alanyl-glutamine, vitamins A and D, pro/prebiotics and also antibiotics. [1] [2] [3] For instance in an urban Bangladeshi slum, EE had a strong impact in oral polio and rotavirus immunization performance 5, 6 but not in those parenterally administrated. 5 Gut microbiome, the administration of pro/prebiotics and their influence in vaccine efficacy has also received considerable attention with varying levels of success. 7 Huda and colleagues analysed microbiome composition in stool samples from 48 Bangladeshi children immunized with oral polio virus (OPV), bacille Calmette-Guérin (BCG), tetanus toxoid (TT), and hepatitis B virus. They noted that Actinobacteria (especially Bifidobacterium longum ssp. infantis) were predominant and positively correlated with OPV, BCG and TT polyclonal T cell proliferation. The authors also found a negative correlation between presence of Enterobacteriales, Pseudomonadales, and Clostridiales and vaccine responses. 8 Another clinical study in India involving 551 infants analysed the influence of a probiotic and also zinc in the immunogenicity of oral Rotarix Rotavirus vaccine. After the normal course of two doses administered at 6 and 10 weeks of age with or without daily zinc (5 mg), probiotic (10 10 Lactobacillus rhamnosus GG) or placebo, a gain in vaccine immunogenicity of 7.5% could be associated with the probiotic (p = 0.066) but not with zinc alone. This modest gain suggests that further studies with similar or other probiotic strains. 9 Also, Parker and colleagues used the same clinical trial setting to evaluate the incidence of 40 bacterial, viral and eukaryotic pathogens as well as the microbiome composition in 325 and 170 infants, respectively. The authors could not find a strong association between vaccine immunogenicity and the microbiome and noted also that colonization by L. rhamnosus GG had been passive rather than successful. Further, the pathogen burden in infants that failed to respond to vaccination was comparable to those that did. 10 Overall, as no single solution can entirely overcome EE, a holistic approach is