Evaluation of non-specific effects of human rotavirus vaccination in medical risk infants

Introduction Rotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence. Aim We assessed the vaccine’s impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction. Methods Epidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon’s index (H′) and Simpson’s index of diversity (D). Results We analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6–59 months old children (H’ p < 0.001: D p < 0.001). In multinomial analysis, G2P[4] (adjusted multinomial odds ratio (aMOR): 9.51; 95% confidence interval (CI): 7.02–12.90), G3P[8] (aMOR: 2.83; 95% CI: 2.17–3.81), G12P[8] (aMOR: 2.46; 95% CI: 1.62–3.73) and G4P[8] (aMOR: 1.42; 95% CI: 1.02–1.96) significantly increased relative to G1P[8]. Conclusions In the context of reduced rotavirus disease incidence, genotype diversity has increased, with a relative change in the dominant genotype from G1P[8] to G2P[4] after vaccine introduction. These changes will need continued surveillance as the number and age of vaccinated birth cohorts increase in the future.

Download Full-text

Genetic characterization of G12P[6] and G12P[8] rotavirus strains in six African countries

10.21203/rs.3.rs-47541/v1 ◽

2020 ◽

Author(s):

Kebareng G. Rakau ◽

Martin M. Nyaga ◽

Maemu P. Gededzha ◽

Jason M. Mwenda ◽

M. Jeffrey Mphahlele ◽

...

Keyword(s):

Amino Acid Level ◽

Sub Saharan Africa ◽

African Countries ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Human Rotavirus ◽

Sub Saharan ◽

The Stability ◽

Long Term Impact

Abstract Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia.Methods: The investigation was carried out by comparing VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and mapping the recognized neutralization epitopes of these strains.Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are homologous at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. The study strains shared a common ancestry with G12 strains circulating globally. Neutralization epitope mapping revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq® P[8] and Rotarix®.Conclusions: It is unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Furthermore, it is too early post vaccine introduction to indicate any effect of vaccine-induced pressure on maintaining the stability of these strains in circulation. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.

Download Full-text

Rotavirus Vaccine Safety and Effectiveness in Infants With High-Risk Medical Conditions

PEDIATRICS ◽

10.1542/peds.2021-051901 ◽

2021 ◽

Author(s):

Josephine A.P. van Dongen ◽

Elsbeth D.M. Rouers ◽

Rob Schuurman ◽

Caterina Band ◽

Shannon M. Watkins ◽

...

Keyword(s):

High Risk ◽

Concomitant Administration ◽

Vaccine Safety ◽

Routine Care ◽

Rotavirus Vaccine ◽

Event Analysis ◽

Term Infants ◽

Medical Risk ◽

Adjusted Risk ◽

Rotavirus Vaccination

OBJECTIVES Rotavirus vaccination has 87% to 100% effectiveness against severe rotavirus acute gastroenteritis (AGE) in healthy infants in high-income countries. Little is known whether infants with medical risk conditions (MRCs) are equally protected and if the vaccine is equally well tolerated. We conducted a quasi-experimental prospective multicenter before-after cohort study to assess the vaccine effectiveness (VE) and safety profile of the human rotavirus vaccine (HRV) among MRC infants that required prolonged or frequent postnatal care. METHODS The Netherlands has no national rotavirus immunization program, but HRV was implemented in routine care for MRC infants in 13 Dutch hospitals. Participants in the before and after cohort, HRV unvaccinated and vaccinated, respectively, were followed for occurrence of (rotavirus) AGE. VE of at least 1 dose was estimated by using time-to-event analysis for severe rotavirus AGE. Vaccine-related serious adverse event (AEs) after HRV were retrieved systematically from medical charts. Solicited AEs after vaccinations were prospectively collected and compared between vaccination time points with or without HRV. RESULTS In total, 1482 high-risk infants with MRC were enrolled, including 631 in the before and 851 in the after cohorts; 1302 infants were premature (88.3%), 447 were small for gestational age (30.2%), and 251 had at least 1 congenital disorder (17.0%). VE against severe rotavirus AGE was 30% (95% confidence interval [CI]: −36% to 65%). Overall, the observed number of rotavirus hospitalizations was low and not significantly different between the cohorts (2 and 2, respectively). The rate of vaccine-related serious AE was 0.24 per 100 vaccine doses. The adjusted risk ratio for any AE after HRV vaccination compared with other routine vaccinations was 1.09 (95% CI: 1.05 to 1.12) for concomitant administration and 0.91 (95% CI: 0.81 to 0.99) for single HRV administration. Gastrointestinal AEs were 10% more frequent after HRV. CONCLUSIONS In contrast to previous findings among healthy term infants, in routine use, HRV offered limited protection to vulnerable medical risk infants. HRV is generally well tolerated in this group in single administration, but when coadministered with routine vaccines, it is associated with higher risk of (mostly gastrointestinal) AE. Our study highlights the importance of studying vaccine performance in subgroups of medically vulnerable infants.

Download Full-text

Protective Immunity and Antibody-Secreting Cell Responses Elicited by Combined Oral Attenuated Wa Human Rotavirus and Intranasal Wa 2/6-VLPs with Mutant Escherichia coli Heat-Labile Toxin in Gnotobiotic Pigs

Journal of Virology ◽

10.1128/jvi.75.19.9229-9238.2001 ◽

2001 ◽

Vol 75 (19) ◽

pp. 9229-9238 ◽

Cited By ~ 48

Author(s):

Lijuan Yuan ◽

Cristiana Iosef ◽

Marli S. P. Azevedo ◽

Yunjeong Kim ◽

Yuan Qian ◽

...

Keyword(s):

Escherichia Coli ◽

Immune System ◽

Oral Dose ◽

Protective Immunity ◽

Mucosal Immune System ◽

Rotavirus Vaccination ◽

Cell Responses ◽

Heat Labile ◽

Human Rotavirus ◽

Protection Rate

ABSTRACT Two combined rotavirus vaccination regimens were evaluated in a gnotobiotic pig model of rotavirus infection and disease and were compared to previously tested rotavirus vaccination regimens. The first (AttHRV/VLP2×) involved oral inoculation with one dose of attenuated (Att) Wa human rotavirus (HRV), followed by two intranasal (i.n.) doses of a rotavirus-like particle (2/6-VLPs) vaccine derived from Wa (VP6) and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were coadministered with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT) adjuvant. For the second regimen (VLP2×/AttHRV), two i.n. doses of 2/6-VLPs+mLT were given, followed by one oral dose of attenuated Wa HRV. To compare the protective efficacy and immune responses induced by the combined vaccine regimens with individual rotavirus vaccine regimens, we included in the experiments the following vaccine groups: one oral dose of attenuated Wa HRV (AttHRV1× and Mock2×/AttHRV, respectively), three oral doses of attenuated Wa HRV (AttHRV3×), three i.n. doses of 2/6-VLPs plus mLT (VLP3×), three i.n. doses of purified double-layered inactivated Wa HRV plus mLT (InactHRV3×), mLT alone, and mock-inoculated pigs. The isotype, magnitude, and tissue distribution of antibody-secreting cells (ASCs) in the intestinal and systemic lymphoid tissues were evaluated using an enzyme-linked immunospot assay. The AttHRV/VLP2× regimen stimulated the highest mean numbers of intestinal immunoglobulin A (IgA) ASCs prechallenge among all vaccine groups. This regimen induced partial protection against virus shedding (58%) and diarrhea (44%) upon challenge of pigs with virulent Wa HRV. The reverse VLP2×/AttHRV regimen was less efficacious than the AttHRV/VLP2× regimen in inducing IgA ASC responses and protection against diarrhea (25% protection rate) but was more efficacious than VLP3× or InactHRV3× (no protection). In conclusion, the AttHRV/VLP2× vaccination regimen stimulated the strongest B-cell responses in the intestinal mucosal immune system at challenge and conferred a moderately high protection rate against rotavirus disease, indicating that priming of the mucosal inductive site at the portal of natural infection with a replicating vaccine, followed by boosting with a nonreplicating vaccine at a second mucosal inductive site, may be a highly effective approach to stimulate the mucosal immune system and induce protective immunity against various mucosal pathogens.

Download Full-text

Genetic characterization of G12P[6] and G12P[8] rotavirus strains collected in six African countries between 2010 and 2014

10.21203/rs.3.rs-47541/v2 ◽

2020 ◽

Author(s):

Kebareng G. Rakau ◽

Martin M. Nyaga ◽

Maemu P. Gededzha ◽

Jason M. Mwenda ◽

M. Jeffrey Mphahlele ◽

...

Keyword(s):

Amino Acid Level ◽

Sub Saharan Africa ◽

African Countries ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Human Rotavirus ◽

Sub Saharan ◽

Long Term Impact

Abstract Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains associated with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia. Methods: The investigation was carried out by comparing partial VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and exploring the recognized neutralization epitopes of these strains. Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are closely related at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. Neutralization epitope screening revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq and Rotarix. Conclusions: At present it appears to be unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.

Download Full-text

The Impact of Visual Stereotypes on Judgments about Rape

Swiss Journal of Psychology ◽

10.1024/1421-0185/a000178 ◽

2016 ◽

Vol 75 (3) ◽

pp. 133-140

Author(s):

Robert Busching ◽

Johannes Lutz

Keyword(s):

Mental Representations ◽

Irrelevant Information ◽

Clear Distinction ◽

Rape Myth ◽

Facial Features ◽

Reverse Correlation ◽

Correlation Technique ◽

Specific Effects ◽

Legal Judgments ◽

The Impact

Abstract. Legally irrelevant information like facial features is used to form judgments about rape cases. Using a reverse-correlation technique, it is possible to visualize criminal stereotypes and test whether these representations influence judgments. In the first step, images of the stereotypical faces of a rapist, a thief, and a lifesaver were generated. These images showed a clear distinction between the lifesaver and the two criminal representations, but the criminal representations were rather similar. In the next step, the images were presented together with rape scenarios, and participants (N = 153) indicated the defendant’s level of liability. Participants with high rape myth acceptance scores attributed a lower level of liability to a defendant who resembled a stereotypical lifesaver. However, no specific effects of the image of the stereotypical rapist compared to the stereotypical thief were found. We discuss the findings with respect to the influence of visual stereotypes on legal judgments and the nature of these mental representations.

Download Full-text