The Centre for Vaccines and Immunology (CVI) was established in 2012, to provide laboratory and epidemiological support to the National Department of Health. The centre serves as the National Surveillance Laboratory and the World Health Organization (WHO) Regional Reference Laboratory for acute flaccid paralysis as well as measles and rubella surveillance. This includes receiving and testing samples from all nine provinces in South Africa. In addition to testing samples from the Southern block countries: Angola, Botswana, Lesotho, Namibia, Madagascar, Mozambique, Malawi, Zambia, Zimbabwe and Swaziland, the centre also conducts other virological and immunological research projects on tuberculosis, viral hepatitis and other vaccine-preventable diseases.
The objectives of CVI are:
- To conduct laboratory-based public health surveillance for acute flaccid paralysis, measles and rubella;
- To provide specialized reference tests for polio and measles surveillance to South Africa and the African continent;
- To initiate applied public health research aimed at vaccine-preventable diseases in South Africa, including hepatitis B; hepatitis C and enteroviruses.
- To apply innovative research regarding the immunology of infectious diseases including HIV, Tuberculosis, and vaccine-preventable disease.
The Centre for Vaccines and Immunology serves as a national and regional reference laboratory for acute flaccid paralysis (AFP) surveillance as part of the Global Polio Eradication Initiative. The laboratory serves seven countries within the southern African region, namely: Angola, Botswana, Lesotho, Mozambique, Namibia, Swaziland and South Africa; processing and testing of more than 2600 stool samples per year. As per WHO recommendations, for any AFP case, stool samples are inoculated into cell cultures. Samples with suggestive cytopathic effects undergo molecular characterisation, including sequencing to confirm the poliovirus serotype.
CVI is the only polio sequencing facility in Africa. In line with the Global Action Plan for poliovirus eradication, the polio laboratory hosts a level three biosafety laboratory (BSL3) to continue high containment work through the final stages of poliovirus eradication. Moreover, the centre has applied to become a Poliovirus Essential Facility (PEF), one of a handful globally.
The centre also acts as a regional reference laboratory for polio-environmental surveillance. We test sewerage samples for poliovirus from Angola, Mozambique and Zambia.
CVI serves as the national referral laboratory for measles and rubella surveillance. In support of the WHO African Region 2020 measles elimination goal, the centre provides serological and molecular testing for measles virus, as well as epidemiological case investigations for the diagnosis of acute measles infection. This data is then shared with the National Department of Health (NDoH), WHO and the Multisectoral National Outbreak Response Team (MNORT). The centre works closely with the National Expanded Programme on Immunisation Task Group to classify cases and monitor outbreaks.
While rubella is not part of the current expanded programme on immunisation, the centre also collates base-line data on rubella incidence to inform decisions for future rubella vaccine implementation. In keeping with rubella incidence, the centre also conducts CRS sentinel site surveillance at 30 sites in all nine provinces. These sites are used to detect and report CRS cases.
CVI in partnership with the National Department of Health, are committed to reach the WHO 2030 viral hepatitis elimination goals. As such, demographic and laboratory data on hepatitis B is being sourced from the NHLS corporate data warehouse. This database surveillance will provide numbers of positive hepatitis B cases in the country, to indicate the national burden of disease. Other research projects regarding hepatitis B as well as hepatitis A and hepatitis C are underway in the centre.
The centre houses a state of the art 18-colour flow cytometer used for cellular immunology as well as two Luminex instruments for multiplexed assays including host tissue typing. CVI collaborates with other researchers from academic institutions to learn more about host responses to HIV, tuberculosis and other pathogens.
South Africa bears a huge burden of tuberculosis, particularly in HIV infected individuals. New host-derived tuberculosis biomarkers which can better detect tuberculosis in HIV-infected individuals could improve detection rates, predict onset of active disease or be used to monitor response to treatment. The centre is evaluating a little-known host biomarker called indoleamine-2,3-dioxygenase (IDO) for diagnosis of tuberculosis in HIV infection from patient plasma. IDO shows promising results for the diagnosis of active TB. As such, the centre further evaluates IDO in an enzyme linked immunosorbent assay (ELISA) as a lower cost, higher throughput method.
Regarding the host immune response to HIV, we are investigating allo-immunity (immunity of one individual against another individual) in couples where one partner has HIV but one partner remained HIV uninfected. HIV allo-immunity was shown relevant to early vaccine trials in animal models but has not been fully explored in humans. The centre is using methods common in transplant laboratories to investigate host response to HIV, which can be thought of as a viral “transplant” from host to recipient.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 was first identified in Wuhan, China at the end of 2019. Since then, there has been rapid and extensive spread throughout the world, leading to a declaration of a COVID-19 pandemic by the World Health Organisation (WHO) on the 11th of March 2020.
Although SARS-CoV-2 is mainly transmitted via respiratory droplets and contact routes, viral RNA (genetic material) may also be detected in the stool of COVID-19 patients. Shedding of virus in stool has been reported even before detecting SARS-CoV-2 in respiratory samples and may continue for a duration of 5 to 35 days after respiratory samples were negative for SARS-CoV-2 RNA. Detection of viral RNA in faeces and urine samples is not an indication that the virus is infectious, but may prove useful for tracking viral spread within communities.
Wastewater-based epidemiology, a method of determining the presence of chemicals, pollutants and microbes in raw wastewater or sewage, has been used as a surveillance tool to detect the presence of certain enteric pathogens such as polioviruses. SARS-CoV-2 shedding in stool has been reported to occur in severe, mild, and asymptomatic infections. The fact that asymptomatic individuals, who are usually missed by clinical and laboratory diagnosis, shed virus in their stool and that it is impractical and expensive to screen everyone, makes water-based epidemiology an attractive tool for SARS-CoV-2 surveillance. This method will provide population-based data for effective modelling and allow determination of COVID-19 prevalence in the absence of extensive testing. SARS-CoV-2 wastewater surveillance can also serve as an early warning sign of the presence of SARS-CoV-2 in certain communities, to allow for targeted testing and interventions, and SARS-CoV-2 WBE can also be used to monitor re-emergence after a country has been declared free of SARS-CoV-2.
To date, several countries have successfully implemented WBE SARS-CoV-2 surveillance using different methods for sewage concentration and SARS-CoV-2 RNA extraction. In South Africa, proof-of-concept has been demonstrated by several laboratories, including the Centre for Vaccines and Immunology at the NICD, who has been processing wastewater samples for SARS-CoV-2. The Centre for Vaccines and Immunology is a WHO poliovirus regional reference laboratory and has previous experience detecting poliovirus from wastewater.
Surveillance of wastewater treatment plants offers an opportunity for near–real-time outbreak data and as an early warning for resurgence of the outbreak. To date, the wastewater-based epidemiology approach has been successfully piloted in developed countries where there is wide coverage of waterborne sanitation, such as the Netherlands, France, United States of America, and more. However, given the varied water and sanitation services delivery mechanisms in South Africa, the country was in a position to pioneer the development and piloting of an all-encompassing water and sanitation-focused approach for the surveillance of COVID-19 spread in less developed communities.
The main objective of the platform is to establish a national surveillance of SARS-CoV-2 in wastewater. This will complement national initiatives by providing early warning of spread of infection, providing information on locations with emerging SARS-CoV-2 infections or fluctuations in viral circulation, and monitoring resurgences. The platform aims to offer strategic responses to curb the escalation of infections in communities, through timely responses.
From November 2020, a one-year pilot phase of a national COVID-19 environmental surveillance system is being implemented. The pilot programme prepares the country to build the logistics and networks to transition into a national programme. The pilot will organise the capacitate a network of laboratories and municipalities to perform SARS-CoV-2 surveillance. Data will be collated by the Centre for Vaccines and Immunology at the NICD using the SACCESS database. Surveillance data from the SACCESS database will be used to supplement patient testing data and identify areas requiring targeted intervention. If the pilot phase is successful, the project will be expanded to national surveillance in 2022.
Expected potential impact of knowledge outputs
Our work will provide valuable information for the management, control, and response to COVID-19 in South Africa. Such data is particularly valuable as it does not depend on health-seeking behaviour of infected individuals or testing patterns. The information generated will be crucial in detecting a possible resurgence of infection or fluctuations, including after potential SARS-CoV-2 vaccine introduction in future.
LEADERSHIP AND TEAM
Dr Melinda Suchard was appointed in 2013 as the Head of the Centre for Vaccines and Immunology. She holds a joint appointment as a lecturer in the Faculty of Health Sciences the University of the Witwatersrand.
She is a ministerial appointed member of the National Advisory Group on Immunization (NAGI), the National Polio Expert Committee (NPEC) and is the president of the South African Immunology Society (SAIS). Her research interests include the investigation of immune-regulation in infectious diseases, methods for monitoring T-cell immunity, and the use of immunological biomarkers for monitoring the tuberculosis disease.