Efficacy of Alum-Adjuvanted Peptide and Carbohydrate Conjugate Vaccine Candidates against Group A Streptococcus Pharyngeal Infection in a Non-Human Primate Model

Author:

Rivera-Hernandez Tania12,Carnathan Diane G.3,Richter Johanna4ORCID,Marchant Patrick5,Cork Amanda J.4ORCID,Elangovan Gayathiri4,Henningham Anna6,Cole Jason N.6,Choudhury Biswa6,Moyle Peter M.7ORCID,Toth Istvan2,Batzloff Michael R.8,Good Michael F.8,Agarwal Paresh5,Kapoor Neeraj5,Nizet Victor6ORCID,Silvestri Guido3,Walker Mark J.4

Affiliation:

1. Consejo Nacional de Humanidades Ciencia y Tecnología, Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico

2. School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia

3. Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA

4. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia

5. Vaxcyte Inc., San Carlos, CA 94070, USA

6. Division of Ob/Gyn & Reproductive Sciences, Vc-Health Sciences-Schools, University of California San Diego, La Jolla, CA 92093, USA

7. School of Pharmacy, The University of Queensland, St. Lucia, QLD 4072, Australia

8. Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia

Abstract

Vaccine development against group A Streptococcus (GAS) has gained traction in the last decade, fuelled by recognition of the significant worldwide burden of the disease. Several vaccine candidates are currently being evaluated in preclinical and early clinical studies. Here, we investigate two conjugate vaccine candidates that have shown promise in mouse models of infection. Two antigens, the J8 peptide from the conserved C-terminal end of the M protein, and the group A carbohydrate lacking N-acetylglucosamine side chain (ΔGAC) were each conjugated to arginine deiminase (ADI), an anchorless surface protein from GAS. Both conjugate vaccine candidates combined with alum adjuvant were tested in a non-human primate (NHP) model of pharyngeal infection. High antibody titres were detected against J8 and ADI antigens, while high background antibody titres in NHP sera hindered accurate quantification of ΔGAC-specific antibodies. The severity of pharyngitis and tonsillitis signs, as well as the level of GAS colonisation, showed no significant differences in NHPs immunised with either conjugate vaccine candidate compared to NHPs in the negative control group.

Funder

National Health and Medical Research Council

National Institutes of Health

Publisher

MDPI AG

Reference37 articles.

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3. Institute for Health Metrics and Evaluation (IHME) University of Washington GBD Results, IHME. Available online: http://vizhub.healthdata.org/gbd-results.

4. Development of Group A Streptococcal Vaccines: An Unmet Global Health Need;Sheel;Expert Rev. Vaccines,2016

5. Update on Group A Streptococcal Vaccine Development;Dale;Curr. Opin. Infect. Dis.,2020

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