Clin Exp Vaccine Res.  2016 Jul;5(2):101-107. 10.7774/cevr.2016.5.2.101.

Accelerating the development of a group A Streptococcus vaccine: an urgent public health need

• Excler JL
• Kim JH

• KMID: 2421556
• DOI: http://doi.org/10.7774/cevr.2016.5.2.101

Abstract

Group A Streptococcus (GAS) infections cause substantial worldwide morbidity and mortality, mostly associated with suppurative complications such as pharyngitis, impetigo, and non-suppurative immune syndromes such as acute rheumatic fever, rheumatic heart disease, and acute post-streptococcal glomerulonephritis. Deaths occur mostly in children, adolescents, and young adults in particular pregnant women in low- and middle-income countries. GAS strains are highly variable, and a GAS vaccine would need to overcome the issue of multiple strains. Several approaches have been used multivalent vaccines using N-terminal polypeptides of different M protein; conserved M protein vaccines with antigens from the conserved C-repeat portion of the M protein; incorporation selected T- and B-cell epitopes from the C-repeat region in a synthetic polypeptide or shorter single minimal B-cell epitopes from this same region; and non-M protein approaches utilizing highly conserved motives of streptococcal C5a peptidase, GAS carbohydrate and streptococcal fibronectin-binding proteins. A GAS vaccine represents urgent need for this neglected disease and should therefore deserve the greatest attention of international organizations, donors, and vaccine manufacturers.

Keyword

Group A Streptococcus; Vaccines; Rheumatic heart disease; M protein; Low- and middle-income countries

MeSH Terms

Adolescent
Child
Epitopes, B-Lymphocyte
Female
Glomerulonephritis
Humans
Impetigo
Mortality
Neglected Diseases
Peptides
Pharyngitis
Pregnant Women
Public Health*
Rheumatic Fever
Rheumatic Heart Disease
Streptococcus*
Tissue Donors
Vaccines
Young Adult
Epitopes, B-Lymphocyte
Peptides
Vaccines

Reference

1. Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet. 2005; 366:155–168.

2. GBD 2013 DALYs and HALE Collaborators. Murray CJ, Barber RM, et al. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition. Lancet. 2015; 386:2145–2191.

3. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380:2095–2128.

4. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005; 5:685–694.

5. Hameed A, Karaalp IS, Tummala PP, et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol. 2001; 37:893–899.

6. Nanna M, Stergiopoulos K. Pregnancy complicated by valvular heart disease: an update. J Am Heart Assoc. 2014; 3:e000712.

7. Zuhlke L, Engel ME, Karthikeyan G, et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J. 2015; 36:1115–1122a.

8. Martin WJ, Steer AC, Smeesters PR, et al. Post-infectious group A streptococcal autoimmune syndromes and the heart. Autoimmun Rev. 2015; 14:710–725.

9. Kaplan EL. Pathogenesis of acute rheumatic fever and rheumatic heart disease: evasive after half a century of clinical, epidemiological, and laboratory investigation. Heart. 2005; 91:3–4.

10. Tandon R, Sharma M, Chandrashekhar Y, Kotb M, Yacoub MH, Narula J. Revisiting the pathogenesis of rheumatic fever and carditis. Nat Rev Cardiol. 2013; 10:171–177.

11. Carapetis JR, Beaton A, Cunningham MW, et al. Acute rheumatic fever and rheumatic heart disease. Nat Rev Dis Primers. 2016; 2:15084.

12. Brown A, McDonald MI, Calma T. Rheumatic fever and social justice. Med J Aust. 2007; 186:557–558.

13. Carapetis JR. The stark reality of rheumatic heart disease. Eur Heart J. 2015; 36:1070–1073.

14. Steer AC, Law I, Matatolu L, Beall BW, Carapetis JR. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis. 2009; 9:611–616.

15. Bessen DE, Carapetis JR, Beall B, et al. Contrasting molecular epidemiology of group A streptococci causing tropical and nontropical infections of the skin and throat. J Infect Dis. 2000; 182:1109–1116.

16. Dale JB, Penfound TA, Chiang EY, Walton WJ. New 30-valent M protein-based vaccine evokes cross-opsonic antibodies against non-vaccine serotypes of group A streptococci. Vaccine. 2011; 29:8175–8178.

17. Smeesters PR, Mardulyn P, Vergison A, Leplae R, Van Melderen L. Genetic diversity of group A Streptococcus M protein: implications for typing and vaccine development. Vaccine. 2008; 26:5835–5842.

18. Hu MC, Walls MA, Stroop SD, Reddish MA, Beall B, Dale JB. Immunogenicity of a 26-valent group A streptococcal vaccine. Infect Immun. 2002; 70:2171–2177.

19. Dale JB, Fischetti VA, Carapetis JR, et al. Group A streptococcal vaccines: paving a path for accelerated development. Vaccine. 2013; 31:Suppl 2. B216–B222.

20. Steer AC, Carapetis JR, Dale JB, et al. Status of research and development of vaccines for Streptococcus pyogenes. Vaccine. 2016; 34:2953–2958.

21. Fox EN, Waldman RH, Wittner MK, Mauceri AA, Dorfman A. Protective study with a group A streptococcal M protein vaccine. Infectivity challenge of human volunteers. J Clin Invest. 1973; 52:1885–1892.

22. Kottlof KL. Streptococcus group A vaccines. In : Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6 ed. Philadelphia, PA: Saunders;2012. p. 1169–1175.

23. Sheel M, Moreland NJ, Fraser JD, Carapetis J. Development of Group A streptococcal vaccines: an unmet global health need. Expert Rev Vaccines. 2016; 15:227–238.

24. McNeil SA, Halperin SA, Langley JM, et al. Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers. Clin Infect Dis. 2005; 41:1114–1122.

25. Kotloff KL, Corretti M, Palmer K, et al. Safety and immunogenicity of a recombinant multivalent group a streptococcal vaccine in healthy adults: phase 1 trial. JAMA. 2004; 292:709–715.

26. Dale JB, Penfound TA, Tamboura B, et al. Potential coverage of a multivalent M protein-based group A streptococcal vaccine. Vaccine. 2013; 31:1576–1581.

27. Batzloff M, Yan H, Davies M, Hartas J, Good M. Preclinical evaluation of a vaccine based on conserved region of M protein that prevents group A streptococcal infection. Indian J Med Res. 2004; 119:Suppl. 104–107.

28. Guilherme L, Fae KC, Higa F, et al. Towards a vaccine against rheumatic fever. Clin Dev Immunol. 2006; 13:125–132.

29. Batzloff MR, Hartas J, Zeng W, Jackson DC, Good MF. Intranasal vaccination with a lipopeptide containing a conformationally constrained conserved minimal peptide, a universal T cell epitope, and a self-adjuvanting lipid protects mice from group A streptococcus challenge and reduces throat colonization. J Infect Dis. 2006; 194:325–330.

30. Batzloff MR, Hayman WA, Davies MR, et al. Protection against group A streptococcus by immunization with J8-diphtheria toxoid: contribution of J8- and diphtheria toxoid-specific antibodies to protection. J Infect Dis. 2003; 187:1598–1608.

31. Pandey M, Langshaw E, Hartas J, Lam A, Batzloff MR, Good MF. A synthetic M protein peptide synergizes with a CXC chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia. J Immunol. 2015; 194:5915–5925.

32. Steer AC, Magor G, Jenney AW, et al. emm and C-repeat region molecular typing of beta-hemolytic Streptococci in a tropical country: implications for vaccine development. J Clin Microbiol. 2009; 47:2502–2509.

33. Steer AC, Batzloff MR, Mulholland K, Carapetis JR. Group A streptococcal vaccines: facts versus fantasy. Curr Opin Infect Dis. 2009; 22:544–552.

34. Fritzer A, Senn BM, Minh DB, et al. Novel conserved group A streptococcal proteins identified by the antigenome technology as vaccine candidates for a non-M protein-based vaccine. Infect Immun. 2010; 78:4051–4067.

35. Bensi G, Mora M, Tuscano G, et al. Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case. Mol Cell Proteomics. 2012; 11:M111.015693.

36. Massell BF, Honikman LH, Amezcua J. Rheumatic fever following streptococcal vaccination: report of three cases. JAMA. 1969; 207:1115–1119.

37. Marijon E, Ou P, Celermajer DS, et al. Prevalence of rheumatic heart disease detected by echocardiographic screening. N Engl J Med. 2007; 357:470–476.

38. Paar JA, Berrios NM, Rose JD, et al. Prevalence of rheumatic heart disease in children and young adults in Nicaragua. Am J Cardiol. 2010; 105:1809–1814.

39. Beaton A, Okello E, Lwabi P, Mondo C, McCarter R, Sable C. Echocardiography screening for rheumatic heart disease in Ugandan schoolchildren. Circulation. 2012; 125:3127–3132.

40. Steer AC, Jenney AW, Kado J, et al. Prospective surveillance of streptococcal sore throat in a tropical country. Pediatr Infect Dis J. 2009; 28:477–482.

41. Parks T, Smeesters PR, Steer AC. Streptococcal skin infection and rheumatic heart disease. Curr Opin Infect Dis. 2012; 25:145–153.

42. Penfound TA, Chiang EY, Ahmed EA, Dale JB. Protective efficacy of group A streptococcal vaccines containing type-specific and conserved M protein epitopes. Vaccine. 2010; 28:5017–5022.

43. Cleary PP, Prahbu U, Dale JB, Wexler DE, Handley J. Streptococcal C5a peptidase is a highly specific endopeptidase. Infect Immun. 1992; 60:5219–5223.

44. Hasty DL, Ofek I, Courtney HS, Doyle RJ. Multiple adhesins of streptococci. Infect Immun. 1992; 60:2147–2152.

45. Steer A. Vaccine development for group A Streptococcus [Internet]. Geneva: World Health Organization;2015. cited 2016 Mar 1. Available from: http://who.int/immunization/research/meetings_workshops/pdvac/en.

46. Remenyi B, Carapetis J, Wyber R, Taubert K, Mayosi BM. World Heart Federation. Position statement of the World Heart Federation on the prevention and control of rheumatic heart disease. Nat Rev Cardiol. 2013; 10:284–292.