Cytomegalovirus among rotavirus vaccinated infants in Zambia and implications for rotavirus vaccine immunogenicity.

Authors: Ms Natasha Laban, Goodier, Martin (London School of Hygiene and Tropical Medicine, London), Bosomprah, Samuel (Centre for Infectious Disease Research in Zambia, University of Ghana), Chilyabanyama, Obvious (Centre for Infectious Disease Research in Zambia), Chibuye, Mwelwa (Centre for Infectious Disease Research in Zambia), Chauwa, Adriance (the University of Zambia, Centre for Infectious Disease Research in Zambia), Simuyandi, Michelo (Centre for Infectious Disease Research in Zambia), Chisenga, Caroline (Centre for Infectious Disease Research in Zambia), Chirwa-Chobe, Masuzyo (Centre for Infectious Disease Research in Zambia), Chipeta, Chikumbutso (Centre for Infectious Disease Research in Zambia) and Chilengi, Roma (Centre for Infectious Disease Research in Zambia)

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Citation Style For This Article: Laban N, Goodier M, Bosomprah S, et al. . Cytomegalovirus among rotavirus vaccinated infants in Zambia and implications for rotavirus vaccine immunogenicity . Health Press Zambia Bull. 2020; 4(4); pp 17

Background

Human cytomegalovirus (HCMV) is a β-herpes virus endemic in developing countries that can be transmitted congenitally or during early infancy and imparts a life-long persistent infection. HCMV has been shown to modulate cellular immunity in infected individuals and therefore HCMV infection in early infancy has the potential to influence the immunogenicity of vaccines administered in the first year of life, including rotavirus vaccines. We aimed to determine HCMV seropositivity in a cohort of mothers and their infants receiving rotavirus vaccination in Zambia.

Methods

We tested available plasma from a total of 82/100 mother-infant pairs enrolled in a randomized controlled trial evaluating two versus three doses of Rotarix®, and from whom infant peripheral blood mononuclear cells were collected, for HCMV seropositivity at infants ages 6-12, 14-18 weeks and 9 months. Plasma was tested for the presence of anti-HCMV IgG (indicating past exposure), and IgM (evidence of recent infection or reactivation) using commercially available enzyme-linked immunosorbent assay (ELISA) based kits (Demeditec Diagnostics GmbH, Germany). HCMV seropositivity was defined as the presence of anti-HCMV IgG or IgM in plasma at a calculated absorption value higher than that of a cut-off standard containing 10 units/ml of anti-HCMV IgG or IgM provided in the ELISA kit.

Results

At baseline, 81/82 mothers (98.78%, 95% CI: 93.39%-99.97%) and 44/82 (53.66%, CI: 42.29%-64.75%) were seropositive for anti-HCMV IgG and anti-HCMV IgM respectively. At pre-vaccination, infant age 6-12 weeks, 77/82 (93.9%, CI: 86.34%-97.99%) and 10/82 (12.2%, CI: 6.01%-21.29%) infants were seropositive for anti-HCMV IgG and anti-HCMV IgM respectively. At 14-18 weeks and 9 months infant age time points, anti-HCMV IgG seropositivity reduced to 85.37% (70/82) (CI: 75.83%-92.2%) and 82.28% (65/79) (CI: 72.06%-89.96%) whereas anti-HCMV IgM seropositivity increased to 20.73% (17/82) (CI: 12.57%-31.11%) and 49.37% (39/79) (CI: 37.92%-60.86%) respectively. 

Conclusion/Recommendations

We documented high maternal and postnatal HCMV seropositivity in Zambia. We found evidence of infant HCMV infection (anti-HCMV IgM) occurring as early as 6-12 weeks of age prior to receipt of rotavirus vaccination which increased substantially within the first 9 months of life. Given the known dominant effects on cellular immunity, we propose that concomitant infant HCMV infection has the potential to influence the immunogenicity of rotavirus vaccines. We will further explore Rotavirus-specific T cell immunity and B-cell mediated antibody responses according to the timing of infant HCMV infection in this cohort. Information on HCMV exposure and its impact on vaccine responses in infants may provide useful insights towards observed vaccine immunogenicity and the need for infant vaccination against HCMV.