Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever

Author(s):Show less -

Blohmke, Christoph J. ^[1] ; Hill, Jennifer ^[1] ; Darton, Thomas C. ^{[1, 2]} ; Carvalho-Burger, Matheus ^[3] ; Eustace, Andrew ^[1] ; Jones, Claire ^[1] ; Schreiber, Fernanda ^[4] ; Goodier, Martin R. ^[5] ; Dougan, Gordon ^[4] ; Nakaya, Helder I. ^[3] ; Pollard, Andrew J. ^[1]

Affiliation

^[1] Univ Oxford, Dept Paediat, Oxford Vaccine Grp, NIHR Oxford Biomed Res Ctr, Oxford - England

^[2] Univ Sheffield, Med Sch, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire - England

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo - Brazil

^[4] Wellcome Trust Sanger Inst, Microbial Pathogenesis Grp, Hinxton - England

^[5] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, London - England

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 8, OCT 12 2017.
• Web of Science Citations: 5

Abstract

The mechanisms by which oral, live-attenuated vaccines protect against typhoid fever are poorly understood. Here, we analyze transcriptional responses after vaccination with Ty21a or vaccine candidate, M01ZH09. Alterations in response profiles were related to vaccine-induced immune responses and subsequent outcome after wild-type Salmonella Typhi challenge. Despite broad genetic similarity, we detected differences in transcriptional responses to each vaccine. Seven days after M01ZH09 vaccination, marked cell cycle activation was identified and associated with humoral immunogenicity. By contrast, vaccination with Ty21a was associated with NK cell activity and validated in peripheral blood mononuclear cell stimulation assays confirming superior induction of an NK cell response. Moreover, transcriptional signatures of amino acid metabolism in Ty21a recipients were associated with protection against infection, including increased incubation time and decreased severity. Our data provide detailed insight into molecular immune responses to typhoid vaccines, which could aid the rational design of improved oral, live-attenuated vaccines against enteric pathogens. (AU)

• FAPESP's process: 12/19278-6 - Systems biology of long non-coding RNAs
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/50828-8 - Systems biology of typhoid fever: unravelling regulation of human host-responses to infection with Salmonella Typhi and live oral vaccination
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Regular Research Grants