Investigation of group A Streptococcus immune responses in an endemic setting, with a particular focus on J8
Patricia Campbell a,b , Hannah Frost b,c , Pierre R. Smeesters b,c,d,e , Joseph Kado f,g,h,i , Michael F.Good j , Michael Batzloff k , Nicholas Geard a,i , Jodie McVernon a,b,m , Andrew Steer b, e, n. Investigation of group A Streptococcus immune responses in an endemic setting, with a particular focus on J8. Volume 36, Issue 50, 29 November 2018, Pages 7618-7624. https://doi.org/10.1016/j.vaccine.2018.10.091
Abstract
Sustained control of group A Streptococcus (GAS) infections in settings of poverty has proven to be challenging, and an effective vaccine may be the most practical long-term strategy to reduce GAS-related disease burden. Candidate GAS vaccines based on the J8 peptide have demonstrated promising immunogenicity in mice, however, less is known about the role of J8 antibodies in the human immune response to GAS infection. We analysed the stimulation of J8 antibodies in response to infection, and the role of existing J8 antibodies in protection against subsequent infection, using data collected in the Fijian population: (1) cross sectional population serosurvey; (2) paired serum collection for assessment of M-specific and J8 antibody responses; and (3) longitudinal assessment of GAS infection and immunity. Median J8 antibody concentrations peaked in the 5–14 year age group, but there was no sustained increase with age. J8 antibody concentration was neither a significant predictor of time to next infection, nor did it show any relationship to the time since last recorded skin infection. Similarly, J8 antibody fold changes over a defined period were associated neither with the time since last skin infection, nor the number of intervening skin infections. While strong M-specific antibody responses were observed for skin infection, similarly strong J8 antibody responses were not observed. There is no indication that antibodies to the J8 antigen would be useful as either a marker of GAS infection or a measure of population immunity, with J8 antibody responses to infection fleeting, if existent at all.
a Victorian Infectious Diseases Reference Laboratory Epidemiology Unit, The Peter Doherty Institute for Infection and Immunity, The Royal Melbourne Hospital and The University of Melbourne, Australia
b Murdoch Children’s Research Institute, The Royal Children’s Hospital, Melbourne, Australia
c Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium
d Department of Pediatrics, Academic Children Hospital Queen Fabiola, Université Libre de Bruxelles, Brussels, Belgium
e Centre for International Child Health, University of Melbourne, Australia
f Department of Paediatrics, Colonial War Memorial Hospital, Fiji
g College of Medicine, Nursing and Health Sciences, Fiji National University, Fiji
h Fiji Rheumatic Heart Disease Control Program, Suva, Fiji
i Telethon Kids Institute, University of Western Australia, Perth, Western, Australia
j Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
k Queensland Institute of Medical Research, Brisbane, Queensland, Australia
l School of Computing and Information Systems, Melbourne School of Engineering, The University of Melbourne, Australia
m Melbourne School of Population and Global Health, The University of Melbourne, Australia
n Department of Paediatrics, University of Melbourne, Royal Children’s Hospital Melbourne, Parkville, Australia