scholarly journals Rotavirus Vaccines: a story of success with challenges ahead

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1517 ◽  
Author(s):  
Miguel O’Ryan

Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries.

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S676-S676
Author(s):  
Jordan Cates ◽  
Avnika Amin ◽  
Jacqueline Tate ◽  
Ben Lopman ◽  
Umesh D Parashar

Abstract Background Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Two rotavirus vaccines – a monovalent vaccine containing a single rotavirus strain (RV1) and a pentavalent vaccine containing 5 rotavirus strains (RV5) – are used in routine immunization programs of nearly 100 countries. Concerns exist that rotavirus vaccines may be less effective against rotavirus strains not contained in the vaccines which could subsequently cause selective pressure and strain replacement. We estimated the vaccine effectiveness (VE) of RV1 and RV5 against vaccine (homotypic) and non-vaccine (partially and fully heterotypic) strains. Methods After conducting a systematic review, we meta-analyzed 31 case-control studies (N=27,293) conducted between 2006 and 2020 using a random-effect regression model. Results In high-income countries, RV1 VE was 10% lower against partially heterotypic (p-value=0.04) and fully heterotypic (p-value=0.10) compared to homotypic strains (homotypic VE: 90% [95% CI: 82, 94]; partially heterotypic VE: 79% [95% CI: 71, 85]; fully heterotypic VE: 80% [95% CI: 65, 88]; Figure 1). In middle-income countries, RV1 VE was 14 to 16% lower against partially heterotypic (p-value=0.06) and fully heterotypic (p-value=0.04) compared to homotypic strains (homotypic VE: 81% [95% CI: 69, 88]; partially heterotypic VE: 67% [95% CI: 54, 76]; fully heterotypic VE: 65% [95% CI: 52, 75]; Figure 1). Strain-specific RV5 VE differences were less pronounced (Figure 2). Limited data were available from low-income countries. Figure 1. Vaccine effectiveness by country income level and strain type, for RV1. Figure 2. Vaccine effectiveness by country income level and strain type, for RV5. Conclusion Vaccine effectiveness of RV1 and RV5 was somewhat lower VE against non-vaccine than vaccine strains. Ongoing surveillance is crucial to continue long-term monitoring for strain replacement, particularly in low-income settings where data are limited. Disclosures All Authors: No reported disclosures


2019 ◽  
Vol 19 (2) ◽  
pp. 81-87
Author(s):  
V. P. Bondarev ◽  
V. A. Shevtsov ◽  
I. N. Indikova ◽  
E. E. Evreinova ◽  
D. V. Gorenkov

Rotavirus infection is a widespread cause of severe gastroenteritis in children in low-income countries. Specific prophylaxis in young children has become the most important means of combating severe rotavirus gastroenteritis. The review presents current data on the molecular biology and genetic diversity of rotaviruses, interaction of viral proteins with host cell receptors, molecular aspects of infectivity and pathogenesis of rotavirus infection, and the development of immunity. It addresses a new approach to the epidemiology of rotavirus infection which regards it as a manageable infection, it illustrates the specificity of the epidemic process based on data gained from extensive experience in vaccination, and summarises relevant information on the introduction of rotavirus vaccines into the international healthcare practice. The paper summarises risks associated with the use of vaccines based on the analysis of WHO statistics, scientific publications on the epidemiology of rotavirus infection, and the results of vaccination. It analyses approaches of the competent authorities of some countries to the tactics of vaccination against rotavirus infection and the WHO stance on the use of existing vaccines for the prevention of rotavirus infection. A conclusion was made that it is necessary to further improve the tactics of vaccine prevention of rotavirus infection in Russia, to study the incidence of idiopathic intussusception, and to conduct further studies aimed at characterisation of existing and newly emerging genotypes of rotavirus.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 341 ◽  
Author(s):  
Olufemi Samuel Folorunso ◽  
Olihile M. Sebolai

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.


2021 ◽  
Author(s):  
Ricardo Aguas ◽  
Anouska Bharath ◽  
Lisa White ◽  
Bo Gao ◽  
Merryn Voysey ◽  
...  

Abstract Background The ongoing COVID-19 pandemic has placed an unprecedented health and economic burden on countries at all levels of socioeconomic development, emphasizing the need to evaluate the most effective vaccination strategy in multiple, diverse environments. The high reported efficacy, low cost, and long shelf-life of the ChAdOx1 nCoV-19 vaccine positions it well for evaluation in different settings. Methods Using data from the ongoing ChAdOx1 nCoV-19 clinical trials, an individual-based model was constructed to predict the 6-month population-level impact of vaccine deployment. A detailed probabilistic sensitivity analysis (PSA) was developed to evaluate the importance of epidemiological, demographic, immunological, and logistical factors in determining vaccine effectiveness. Using representative countries, logistical plans for vaccination rollout at various levels of vaccine availability and delivery speed, conditional on vaccine efficacy profiles (efficacy of the booster dose, time interval between doses, and relative efficacy of the first dose) were explored.Findings and Interpretation Our results highlight how expedient vaccine delivery to high-risk groups is critical in mitigating COVID-19 disease and mortality. In scenarios where the number of vaccine doses available is insufficient for high-risk groups (those aged more than 65 years) to receive two vaccine doses, administration of a single dose of vaccine is optimal. This effect is consistent even when vaccine efficacy after one dose is just 75% of the levels achieved after two doses. These findings offer a nuanced perspective of the critical drivers of COVID-19 vaccination effectiveness and can inform optimal allocation strategies. These are relevant to high-income countries with a large high-risk group population as well as to low-income countries with younger populations, where the cost and logistical challenges of procuring and delivering two doses for each citizen represent a significant challenge.


2020 ◽  
Vol 4 (2) ◽  
pp. 128-139
Author(s):  
Masunga K Iseselo ◽  
Edith AM Tarimo ◽  
Eric Sandstrom ◽  
Asli Kulane

Background: HIV vaccine efficacy trials require the active participation of volunteers who are committed and adherent to the study protocol. However, information about the influence of Injecting Drug Users (IDUs) to participate in HIV vaccine efficacy trials in low-income countries is inadequate. The present study explored the factors that motivate or hinder IDUs from participating in HIV vaccine efficacy trials in Dar es Salaam, Tanzania. Methods: A qualitative descriptive study design was employed among IDUs at Muhimbili National Hospital (MNH). A purposeful sampling technique was used to recruit the participants. Three (3) focus group discussions (FGDs) and 10 In-Depth Interviews (IDIs) were used to collect the data. The data from participants were audio-recorded, transcribed, and analysed using the content analysis approach. Findings: The participants reported that altruism and the desire to reduce risks of HIV infection were the motivators to participate in hypothetical HIV vaccine trials. In addition, participants reported to consult close relatives towards motivation to participate in the vaccine trial. In contrast, the perceived fear of vaccine side effects, lack of information about HIV vaccine studies, and HIV-related stigma towards participants were described as barriers to participate in the HIV vaccine trials. Conclusion: Participation in a hypothetical HIV vaccine trial among IDUs is influenced by positive and negative factors. Actual recruitment plans could be made through a better explanation of HIV vaccine trials, the expected individual and collective benefits associated with the trials. Community involvement and sensitisation is likely to enhance participation in future HIV vaccine trials in Tanzania.


Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 795
Author(s):  
Jaime MacDonald ◽  
Michelle J. Groome ◽  
Janet Mans ◽  
Nicola Page

Gastroenteritis is a preventable cause of morbidity and mortality worldwide. Rotavirus vaccination has significantly reduced the disease burden, but the sub-optimal vaccine efficacy observed in low-income regions needs improvement. Rotavirus VP4 ‘spike’ proteins interact with FUT2-defined, human histo-blood group antigens on mucosal surfaces, potentially influencing strain circulation and the efficacy of P[8]-based rotavirus vaccines. Secretor status was investigated in 500 children <5 years-old hospitalised with diarrhoea, including 250 previously genotyped rotavirus-positive cases (P[8] = 124, P[4] = 86, and P[6] = 40), and 250 rotavirus-negative controls. Secretor status genotyping detected the globally prevalent G428A single nucleotide polymorphism (SNP) and was confirmed by Sanger sequencing in 10% of participants. The proportions of secretors in rotavirus-positive cases (74%) were significantly higher than in the rotavirus-negative controls (58%; p < 0.001). The rotavirus genotypes P[8] and P[4] were observed at significantly higher proportions in secretors (78%) than in non-secretors (22%), contrasting with P[6] genotypes with similar proportions amongst secretors (53%) and non-secretors (47%; p = 0.001). This suggests that rotavirus interacts with secretors and non-secretors in a VP4 strain-specific manner; thus, secretor status may partially influence rotavirus VP4 wild-type circulation and P[8] rotavirus vaccine efficacy. The study detected a mutation (rs1800025) ~50 bp downstream of the G428A SNP that would overestimate non-secretors in African populations when using the TaqMan® SNP Genotyping Assay.


The Lancet ◽  
2007 ◽  
Vol 370 (9601) ◽  
pp. 1739-1740 ◽  
Author(s):  
Keith Grimwood ◽  
Julie E Bines

PLoS Medicine ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. e1003720
Author(s):  
Sheila Isanaka ◽  
Souna Garba ◽  
Brian Plikaytis ◽  
Monica Malone McNeal ◽  
Ousmane Guindo ◽  
...  

Background Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. Methods and findings We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. Conclusions This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. Trial registration ClinicalTrials.gov NCT02145000.


Author(s):  
Davor Petrović ◽  
Vida Čulić ◽  
Zofia Swinderek-Alsayed

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.


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