Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

AbstractIdentifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

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Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants: a prospective cohort study

10.1101/2020.11.02.20224576 ◽

2020 ◽

Author(s):

Edward P. K. Parker ◽

Christina Bronowski ◽

Kulandaipalayam Natarajan C. Sindhu ◽

Sudhir Babji ◽

Blossom Benny ◽

...

Keyword(s):

Low Income ◽

Early Life ◽

Maternal Antibodies ◽

Low Income Countries ◽

Rotavirus Vaccine ◽

Specific Antibodies ◽

Environmental Enteric Dysfunction ◽

The Uk ◽

Antibody Levels ◽

Microbiota Diversity

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. We measured maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. ORV shedding and seroconversion rates were significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk were negatively correlated with ORV response in India and Malawi, and this was mediated partly by a reduction in ORV replication. In the UK, ORV replication was not inhibited despite comparable maternal antibody levels. In both India and Malawi, pre-vaccination microbiota diversity was negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

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Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

Vaccine ◽

10.1016/j.vaccine.2020.01.097 ◽

2020 ◽

Vol 38 (13) ◽

pp. 2870-2878 ◽

Cited By ~ 1

Author(s):

James A. Church ◽

Bernard Chasekwa ◽

Sandra Rukobo ◽

Margaret Govha ◽

Benjamin Lee ◽

...

Keyword(s):

Rotavirus Vaccine ◽

Vaccine Immunogenicity

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The Impact of Improved Water, Sanitation, and Hygiene on Oral Rotavirus Vaccine Immunogenicity in Zimbabwean Infants: Substudy of a Cluster-randomized Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciz140 ◽

2019 ◽

Vol 69 (12) ◽

pp. 2074-2081 ◽

Cited By ~ 4

Author(s):

James A Church ◽

Sandra Rukobo ◽

Margaret Govha ◽

Benjamin Lee ◽

Marya P Carmolli ◽

...

Keyword(s):

Primary Outcome ◽

Oral Vaccine ◽

Geometric Mean ◽

Developed Countries ◽

Absolute Difference ◽

Rotavirus Vaccine ◽

Sanitation And Hygiene ◽

Vaccine Immunogenicity ◽

Cluster Randomized ◽

The Impact

Abstract Background Oral vaccines have lower efficacy in developing compared to developed countries. Poor water, sanitation, and hygiene (WASH) may contribute to reduced oral vaccine immunogenicity. Methods We conducted a cluster-randomized 2 × 2 factorial trial in rural Zimbabwe. Pregnant women and their infants were eligible if they lived in clusters randomized to (1) standard of care (52 clusters); (2) improved infant feeding (53 clusters); (3) WASH: ventilated improved pit latrine, 2 hand-washing stations, liquid soap, chlorine, infant play space, and hygiene counseling (53 clusters); or (4) feeding plus WASH (53 clusters). This substudy compared oral rotavirus vaccine (RVV) seroconversion (primary outcome), and seropositivity and geometric mean titer (GMT) (secondary outcomes), in WASH vs non-WASH infants by intention-to-treat analysis. Results We included 801 infants with documented RVV receipt and postvaccine titer measurements (329 from 84 WASH clusters; 472 from 102 non-WASH clusters); 328 infants with prevaccination titers were included in the primary outcome. Thirty-three of 109 (30.3%) infants in the WASH group seroconverted following rotavirus vaccination, compared to 43 of 219 (19.6%) in the non-WASH group (absolute difference, 10.6% [95% confidence interval {CI}, .54%–20.7%]; P = .031). In the WASH vs non-WASH groups, 90 of 329 (27.4%) vs 107 of 472 (22.7%) were seropositive postvaccination (absolute difference, 4.7% [95% CI, –1.4% to 10.8%]; P = .130), and antirotavirus GMT was 18.4 (95% CI, 15.6–21.7) U/mL vs 14.9 (95% CI, 13.2–16.8) U/mL (P = .072). Conclusions Improvements in household WASH led to modest but significant increases in seroconversion to RVV in rural Zimbabwean infants. Clinical Trials Registration NCT01824940.

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