Human Immunity to Potential Group A Streptococcal Vaccine Antigens in Subjects at High Risk for Rheumatic Heart Disease

Project: SFRN


  • James Dale (PI)


Rheumatic heart disease (RHD) is the most common cardiovascular disease in children and young adults in the world today. The overall goal of this project is to develop safe, effective, and affordable vaccines to prevent group A streptococcal (GAS) infections. Vaccine prevention of GAS infections is considered to be the most promising long-term approach to the prevention of acute rheumatic fever (ARF) and RHD. The project is a prospective longitudinal study of subjects in Cape Town, South Africa, ages 5-15, to assess new pharyngeal acquisitions of GAS and immune responses to a comprehensive panel of specific GAS antigens, most of which are considered potential vaccine components. Little is known about the human immune response to these antigens following natural infection with GAS. The study provides a unique opportunity to identify potentially protective immune responses following natural infection in school-age children from a population at high risk for the development of ARF and RHD. We will enroll 300 participants, aged 5-15 years, from two neighborhoods in Cape Town. Participants will be evaluated at baseline and every 2 months, over a 24-month period of observation, with serial throat cultures for GAS and serum samples for immunological studies. Serum antibody levels against a panel of antigens will be assessed, with particular attention to immune responses following new pharyngeal acquisitions of GAS. The aims of the study are: Aim 1, assess the frequency, emm type, and duration of persistence of new pharyngeal acquisitions of GAS, and Aim 2, determine the kinetics and antigen specificity of serum immune responses following new pharyngeal acquisitions of GAS. Data analysis will assess: 1) the frequency, emm type, percent symptomatic, and duration of carriage of new GAS acquisitions, 2) the immunogenicity of potential vaccine antigens following naturally acquired symptomatic or asymptomatic GAS infection, 3) the percent of subjects that experience immunologically significant GAS acquisitions (infections) vs. carriage, 4) whether preexisting levels of antibodies against specific GAS antigens are associated with no new GAS acquisition's during the 24-month observation period, and 5) the immune profile of subjects with recurrent GAS acquisitions as indicators of protective and non-protective antibodies. The results of this study will be used to inform the design and development of a broadly protective vaccine that will ultimately be deployed globally.
Award amount$1,003,927.00
Award date07/01/2017
Program typeStrategically Focused Research Network
Award ID17SFRN33670451
Effective start/end date07/01/201706/30/2021