Hanlon, P. et al. Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants. Lancet 329, 1342-1345
ABSTRACT A randomised, controlled trial of bovine rotavirus vaccine was undertaken in Gambian infants. Three doses were administered, from the age of ten weeks, concurrently with oral or killed polio vaccine. Prevaccination rotavirus neutralising antibody levels were high. 84/185 infants (45%) showed an increase in neutralising antibody titre after receiving rotavirus vaccine, compared with 20/91 (22%) unvaccinated infants. Clinical rotavirus infection was detected in 24/78 (31%) children in the rotavirus/oral polio group, 34/83 (41%) children in the placebo/oral polio group, and 23/92 (25%) children in the rotavirus/killed polio group, giving an overall vaccine efficacy of 33% (95% CI 4-53%). RIT 4237 did not appear to reduce the severity of clinical infections. Most cases (92%) were caused by rotaviruses with short RNA electropherotypes. Serological responses to rotavirus vaccination appeared unaffected by the concurrent administration of oral polio vaccine. Lower types 1 and 3 polio antibody levels were found in children who received oral polio and rotavirus vaccines but the differences were not statistically significant.
- SourceAvailable from: Venkata Raghava Mohan
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- "Similarly, in clinical trials conducted mainly in the USA and Finland, RV5 was 96% (95% CI: 91–98%) efficacious against hospitalizations due to rotavirus gastroenteritis caused by G1–G4 strains, 94% (95% CI: 89–97%) against emergency department visits, and 86% (95% CI: 74–93%) against office visits . Because live oral vaccines, including earlier candidate rotavirus vaccines, have a history of performing less well in developing countries        , WHO specifically recommended that efficacy trials of both RV1 and RV5 be conducted in low income countries of Africa and Asia before issuing a global recommendation for rotavirus vaccine use. Vaccine efficacy was modest in these trials. "
ABSTRACT: Rotavirus vaccines are being introduced in several low- and middle-income countries across the world with and without support from the GAVI Alliance. India has the highest disease burden of rotavirus based on morbidity and mortality estimates and several indigenous vaccine manufacturers are developing rotavirus vaccines. One candidate has undergone phase III testing and others have completed evaluation in phase II. Global data on licensed vaccine performance in terms of impact on disease, strain diversity, safety and cost-effectiveness has been reviewed to provide a framework for decision making in India.Vaccine 08/2014; 32:A171–A178. DOI:10.1016/j.vaccine.2014.03.029 · 3.62 Impact Factor
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- "Geographical variations in responses to vaccines have been reported; for example, protection against pulmonary tuberculosis by the Bacillus Calmette–Guérin (BCG) vaccine varies from 0% to 80% in adults, with higher protection in populations living at higher latitudes , or the rotavirus vaccine which provided little protection against rotavirus diarrhea in Gambian infants but showed promising results in Europe . With respect to immunological changes following vaccination, a study in infants and adolescents from the United Kingdom showed that BCG vaccination induced a marked increase in interferon-γ (IFN- γ) response to Mycobacterium tuberculosis purified protein derivative (Mtb PPD), but not in infants and adolescents from Malawi . "
ABSTRACT: Although differences in immunological responses between populations have been found in terms of vaccine efficacy, immune responses to infections and prevalence of chronic inflammatory diseases, the mechanisms responsible for these differences are not well understood. Therefore, innate cytokine responses mediated by various classes of pattern-recognition receptors including Toll-like receptors (TLR), C-type lectin receptors (CLRs) and nucleotide-binding oligomerisation domain-like receptors (NLRs) were compared between Dutch (European), semi-urban and rural Gabonese (African) children. Whole blood was stimulated for 24 hours and the pro-inflammatory tumor necrosis factor (TNF) and the anti-inflammatory/regulatory interleukin-10 (IL-10) cytokines in culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Gabonese children had a lower pro-inflammatory response to poly(I:C) (TLR3 ligand), but a higher pro-inflammatory response to FSL-1 (TLR2/6 ligand), Pam3 (TLR2/1 ligand) and LPS (TLR4 ligand) compared to Dutch children. Anti-inflammatory responses to Pam3 were also higher in Gabonese children. Non-TLR ligands did not induce substantial cytokine production on their own. Interaction between various TLR and non-TLR receptors was further assessed, but no differences were found between the three populations. In conclusion, using a field applicable assay, significant differences were observed in cytokine responses between European and African children to TLR ligands, but not to non-TLR ligands.PLoS ONE 04/2014; 9(4):e95241. DOI:10.1371/journal.pone.0095241 · 3.23 Impact Factor
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- "Efficacy trials conducted in both developed and less-developed nations have shown that both Rotarix and RotaTeq are highly protective against severe rotavirus disease. However, the efficacies of each against rotaviruses belonging to emerging serotypes are yet to be determined and neither has been evaluated in Third World nations where earlier live rotavirus vaccine candidates have failed (De Mol et al., 1986; Georges-Courbot et al., 1991; Hanlon et al., 1987; Lanata et al., 1989). Thus, there is a need to develop and evaluate second generation rotavirus vaccines that are based on a different paradigm, that is, they are non-living. "
ABSTRACT: The only lymphocytes required for protection against fecal rotavirus shedding after intranasal immunization of BALB/c (H-2(d)) mice with a chimeric rotavirus VP6 protein (MBPColon, two colonsVP6) and the mucosal adjuvant LT(R192G) are CD4(+) T cells. The purpose of this study was to identify CD4(+) T cell epitopes within VP6 that might be responsible for this protection. To make this determination, spleen cells obtained from BALB/c mice following intranasal immunization with MBPColon, two colonsVP6/LT(R192G) were stimulated in vitro with either MBPColon, two colonsVP6 or overlapping VP6 peptides containing <or=30 amino acids (AA). The numbers of memory (CD44(high)) CD4(+) T cells stimulated to produce T(H)1 and T(H)17 cytokines (IFNgamma and IL-17), as well as the quantities of these cytokines released into the cell supernatants, were then measured relative to those produced in mock-stimulated cells from the same animals. One epitope expected to be found was the VP6 14-mer AA(289-302), previously identified as a CD4(+) T cell epitope in H-2(d) mice. This was not observed but instead the only VP6 epitope identified was AA(242-259), the dominant CD4(+) T cell epitope previously reported after oral, live rotavirus immunization.Virology 07/2007; 363(2):410-8. DOI:10.1016/j.virol.2007.01.041 · 3.32 Impact Factor