Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines

Abstract

Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix^®, RotaTeq^®, Rotavac^®, and RotaSIIL^®) have been developed and licensed to be used against all forms of rotavirus-associated infection. The efficacy of these vaccines is more obvious in the high-income countries (HIC) compared with the low- to middle-income countries (LMICs); however, the impact is far exceeding in the low-income countries (LICs). Despite the rotavirus vaccine efficacy and effectiveness, more than 90 countries (mostly Asia, America, and Europe) are yet to implement any of these vaccines. Implementation of these vaccines has continued to suffer a setback in these countries due to the vaccine cost, policy, discharging of strategic preventive measures, and infrastructures. This review reappraises the impacts and effectiveness of the current live-attenuated oral rotavirus vaccines from many representative countries of the globe. It examines the problems associated with the low efficacy of these vaccines and the way forward. Lastly, forefront efforts put forward to develop initial procedures for oral rotavirus vaccines were examined and re-connected to today vaccines.

Keywords: diarrhoea; gastroenteritis; hospitalisation; immune-response; intussusception; rotavirus; rotavirus vaccines; seroconversion; vaccine effectiveness; vaccine efficacy.

Figure 1

Detail illustration of rotavirus particle and its segmented dsRNA genome encoding protein: (a) Electrophoretic pattern of rotavirus group A (RVA) individual segmented genomic RNA with their corresponding encoded proteins. The proximity of segments 7, 8, and 9 represents the identity of rotavirus electrophoretic pattern; (b) cryo-electron microscopy reconstruction (CEMR) of the rotavirus triple-layered particles (TLPs) with the spike-like protein VP4 and the outer-layer glycoprotein VP7 (shaded in yellow) with specific localisation of transcriptional pores—I, II, and III; (c) a semi-longitudinal section of TLPs showing the inner capsid (VP6) and core protein (VP2) layers and the transcriptional enzymes accessories (VP1 and VP3) enclosed by the VP2 core protein; (d) genomic organisation in rotavirus core protein (VP2) with intricate transcriptional enzymes enclosed inside the protein coat; (e) complete longitudinal section of rotavirus TLPs showing the chronological arrangement of the segmented genomes (VP1 to NSP5/6); (f,g) model from CEMR of transcribing double-layered particles (DLPs) showing the endogenous transcription, which results in the simultaneous release of the transcribed mRNAs. Figures adapted and modified from [12,13] with permissions.

Figure 2

Terminal oligosaccharides of histo-blood group antigens (HBGAs) receptors that facilitate rotavirus VP8* binding. Terminal fucose is catalysed by α-1,2-fucosyltransferase 2 encoded by the FUT2 gene, generally referred to as “secretor” to form an H-type glycol-receptor, which can remain unmodified as type O⁺ secretor. However, when terminal fucose is catalysed by α-1,4-fucosyltransferase 3 encoded by the FUT3 gene and remained unmodified, it becomes type O^- non-secretor. Subsequent modification produced A-type, B-type, Lewis, A-Lewis, and B-Lewis. Terminal -GalNAc in the A-type makes it vulnerable to many rotavirus strains and enhances inter-species transmission.