Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

glycans (lacto-N-biose and N-acetyllactosamine, respectively) that become less prevalent with age. 15 Also, infection with the common VP4 P [8] genotype correlates with HBGA secretor status. For instance, loss of FUT2 function leads to virtually no infection with P [8] strains in countries like Vietnam 19 and the USA, 20 but not in Tunisia where among 32 children infected, P [8] was present in both secretor and non-secretors that are positive for Lewis antigen. 21 Also, in Pakistan, a study comprising 181 infants that were seronegative before immunization with three courses of a G1P [8] vaccine strain indicated that 19% (10/ 54) of responders were non-secretors whereas secretors were 51% (20/39) type O and 30% (26/88) were types A, B or AB. 22 In addition, 18 P [6] infections (from a total of 27) were seen in predominantly Lewis-negative children (a frequent phenotype in African populations), while 27 Lewis-negative individuals were resistant to P [8] infection (0 in a total of 27 children). The same study noted that all 22 children in Nicaragua and 27 in Burkina Faso infected with P[8] strains were secretor Lewis positive. 23 Rotavirus can also enter our bodies via M cells 24 that are located within follicle-associated epithelia (FAE). M cells possess structural and functional traits that allow transport of antigens to the adjacent mucosal-associated lymphoid tissue. 25 In the small intestine, M cells are concentrated around aggregates of lymphoid follicles called Peyer's Patches (PP). In infected individuals, production of mucus by the FAE is also reduced which facilitates uptake of pathogens by M cells and further processing by the underlying mucosal immune system. 26 Overall, there is a great diversity in Rotavirus strains with a limited number of genotypes playing a dominant role. These have largely defined the makeup of Rotavirus vaccines to date. Host genetics also impact viral entry and as such vaccine development could benefit from genotypic screening of regional and national populations. Similarly, as in the case of influenza, regular monitoring of prevalent viral strains could lead to better adjustments of vaccine to patients' needs, although in the case of Rotavirus this aspect has not been clearly established. Finally, taking into account the capacity of M cells for uptake of antigens, optimizing delivery to these could increase vaccine efficiency (see below).