Sex Differences in Vaccine-Specific and Heterologous Immunity Following Administration of Measles and /or DtwP Vaccines to Nine Month-Old Gambian Infants

Noho-Konteh, Fatou (2015). Sex Differences in Vaccine-Specific and Heterologous Immunity Following Administration of Measles and /or DtwP Vaccines to Nine Month-Old Gambian Infants. MPhil thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f04c

Abstract

The expanded programme of immunization was introduced in The Gambia over 30 years ago, using empirically developed vaccines with limited understanding of exactly how they work. Observational studies showing vaccines have heterologous beneficial or deleterious effects on disease susceptibility, dependent on sex, have been controversial, with no immunological data to support these epidemiological findings. The live measles vaccine (MV) seems to have beneficial protective effects, while diphtheria, tetanus, whole cell pertussis (DTwP) vaccine increases disease susceptibility, both effects being more prominent in females. These effects are modified when the vaccines are given simultaneously.

This thesis describes the results of a randomized trial primarily aimed at studying the heterologous effects of MV and DTwP vaccination of 9 month old Gambian infants. Assays included multiplex cytokine analysis of culture supernatants, flow cytometric intracellular staining, vaccine antibody assays, and whole transcriptome microarray analysis.

Measles and DTwP antibodies were not affected by combining vaccines or by gender. When DTwP is given with MV, the measles-specific response was skewed away from a protective CD8 IFN-γ response, while TT responses become more pro-inflammatory suggesting that MV has an adjuvant effect on DTwP immunity.

A striking finding was the immunosuppressive effect of DTwP, particularly in females. There was a reduction in pro-inflammatory cytokines and reduced IFN-γ:IL-10 ratios in aCD3/28 cultures, alongside down-regulated interferon response gene pathways, and increased innate IL-10 production in DTwP vaccinated females. By contrast, DTwP vaccinated males a more pro-inflammatory profile than females with only upregulated genes post-vaccination. Males vaccinated with MV+DTwP were less pro-inflammatory than females, and had only down-regulated genes suggesting this combination had opposite effects in males and females.

The results provide plausible immunological explanations for the observed beneficial and deleterious effects of MV and DTwP respectively. These will now need to be tested in carefully designed prospective studies.

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