Association of Antibody-Dependent Neutrophil Phagocytosis With Distinct Antibody Glycosylation Profiles Following Typhoid Vaccination

M Johnson ,Mila Shakya,Lisa Stockdale,Sabina Dongol,Manfred Wuhrer,Merryn Voysey,Buddha Basnyat,Andrew J Pollard,Noortje De Haan,Dikshya Pant,Katherine Theiss-Nyland,Jan Nouta,Elizabeth Jones ,Koeleman Cam ,Jenny Clarke ,Sarah Kelly ,Shrijana Shrestha ,Spyridoula Marinou ,Chunlin Jin ,A Karkey ,Jennifer Hill ,Rachel Colin-Jones

doi:10.3389/fitd.2021.742804

Abstract

Typhoid Vi-conjugate vaccines (Vi-TCV) have been developed to control typhoid fever in children in endemic regions. Previously, in a human challenge model of typhoid, Vi-TCV was administered prior to deliberate ingestion of Salmonella Typhi by healthy adult volunteers in the UK. Vi-specific antibody-dependent neutrophil phagocytosis (ADNP) was associated with protection against enteric fever in this model, but it is not known if ADNP is induced by vaccination of children. We measured ADNP in a cohort of Nepalese children receiving a Vi-TCV in a field study to investigate whether functional antibody responses were also present in children in an endemic setting. Furthermore, we investigated relationships between the functional antibody measures and other properties of the antibody response, including Vi-IgG and IgA titres, and Fc region glycosylation. Antibody-dependent neutrophil phagocytosis significantly increased in children aged 9 months to 15 years between the day of vaccination and 28 days following administration of Vi-TCV (D28). The magnitude of ADNP was also comparable with the levels of ADNP induced by plasma from vaccinated UK adults. Neither IgG nor IgA antibody titres significantly correlated with ADNP scores at D28; however, increased vaccine-induced ADNP was associated with decreased levels of IgG1 sialylation. These data suggest that vaccination with Vi-TCV produces functional antibody responses in children, which associate with specific glycosylation patterns of the Fc region.

Highlights

Typhoid fever is a gastrointestinal infection caused by the bacterium Salmonella enterica serovar Typhi
antibody-dependent neutrophil phagocytosis (ADNP) Increases From Baseline 28 Days After Vi-TCV Vaccination in Nepalese Children, and Is Comparable to Responses in UK Adults
To assess the Vi-specific ADNP response in children vaccinated with Vi-TCV in Nepal, plasma samples from children vaccinated in the TyVAC study were analysed for their capacity to induce neutrophil phagocytosis at baseline and 28 days post-vaccination (n = 77)

Summary

Introduction

Typhoid fever is a gastrointestinal infection caused by the bacterium Salmonella enterica serovar Typhi Typhoid fever predominately affects children in low and middle-income countries where access to clean drinking water is limited [1, 2]. In 2017 there were an estimated 10.9 million cases of typhoid fever resulting in approximately 116,000 deaths [3]. Typhi is the dominant cause of bloodstream bacterial infections [4], and annual incidence has been estimated up to 449 cases per 100,000 (95% CI, 383 to 521) [3]. Given the high prevalence of typhoid fever, and increasing antimicrobial resistance, effective vaccination campaigns are needed more than ever [7, 8]. Typhi, was approved by the WHO, and recently demonstrated clinical efficacy of 81.6% in a field study involving over 20,000 Nepalese children [9, 10]

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Results

Conclusion