Serological tools for COVID-19 control and vaccine roll-out in Southeast Asia

Lead Research Organisation: London School of Hygiene & Tropical Medicine
Department Name: Infectious and Tropical Diseases

Abstract

The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused immeasurable burden on economies and public health globally, including in Asia. New diagnostics for detecting the present and past exposure to the virus have been developed, and vaccines are emerging for clinical evaluation and roll-out. As the number of cases plateau, the exit strategy of Governments will involve the use of surveillance and contact tracing to limit the damage of future sporadic outbreaks in the short to medium term, while vaccination will ideally lead to elimination. However, many of the tests and vaccines under evaluation are based on the same biological targets, and infection control activities will need to distinguish immune responses to vaccines and those elicited by SARS-CoV-2 infection, which cannot yet be achieved with current front-line rapid testing kits. With this in mind, we propose to investigate alternative immunological targets arising from LSHTM modelling, informatic tools and laboratory work. These targets will be assessed within ongoing collaborations with government research institutes and hospitals in Thailand and The Philippines, who are at the forefront of clinical management and infection control in the COVID-19 response. These sites have pre-existing biological samples and data collected for diagnosis and treatment that will be used in the proposed project. We will evaluate new biological targets and establish assays that can be implemented by these countries to assist a surveillance system to monitor the progress of vaccination and SARS-CoV-2 elimination in the community. This will provide vital data for the direction of vaccine rollout and containment strategy. Most importantly, the tools developed can be easily implemented across other LMIC countries with a minimal laboratory set-up. With this, our goal, is to make a lasting contribution to Southeast Asian COVID-19 surveillance infrastructure, thereby improving the health and economy of the nations.

Technical Summary

The unprecedented spread of SARS-CoV-2 has led to the rapid development of diagnostics of active disease, serological assays for infection exposure, and the evaluation of potential vaccines in clinical trials. Governments have begun to consider and evaluate possible exit strategies underpinned by surveillance and vaccination. Surveillance, utilising mass testing and contact tracing, will limit the damage of future sporadic outbreaks in the short term, while vaccination will ideally lead to elimination. To date, many rapid serological tests and vaccines under evaluation are based on the same SARS-CoV-2 targets (e.g. spike protein), but surveillance activities will need to distinguish vaccine from natural infection. Research supporting the deployment of these measures will prove vital to their timely implementation and long-term efficacy.

Our project builds on an existing collaboration of LSHTM with its genomic-immunology tools for the active surveillance of SARS-CoV-2, and the Thailand Ministry of Public Health (MOPH) and Philippines Department of Health (DOH), who are at the forefront of clinical management of COVID-19 and involved in their countries infection control taskforces. We will evaluate new serological targets and establish assays that can be implemented to assist a surveillance system to monitor the progress of vaccination and SARS-CoV-2 elimination in the community. To achieve this, we will apply tools that can differentiate immune responses to vaccines and those elicited by SARS-CoV-2 infection; something that cannot yet be achieved with current front-line rapid testing kits. This will provide vital data for the direction of vaccine rollout and containment strategy, develop deployable tools, and make a lasting contribution to Thailand and Philippines COVID-19 surveillance infrastructure.

Publications

10 25 50
 
Description There are the scientific insights and lessons concerning the utility of genomics, including identification of mixed infections, which are informing infection control. The serological analysis has provided insights into which vaccines have induced the greatest and most long-lasting immune responses.
Exploitation Route The Ministry of Public Health in Thailand is directly involved in this work, and is implementing the assays to understand patterns of infection, as well as genome sequencing to understand any circulating variants.
Sectors Healthcare

 
Title COVID-19 sample processing, serological and sequencing analysis 
Description This is a set of protocols for COVID-19 serum processing for serological characterisation and genome sequencing. Statistical and bioinformatic tools and pipelines for the analysis of the resulting data have been developed and implemented. 
Type Of Material Biological samples 
Year Produced 2020 
Provided To Others? No  
Impact This will facilitate local COVID-19 serological and transmission analysis. 
 
Title Protocols for serological evaluations and SARS-CoV-2 genomic sequencing 
Description The serological assay is built on the Luminex xMAP multiplex platform, enabling the high-throughput screening of 20+ antigens targeting SARS-CoV-2, other prevalent human Coronavirus species, and prevalent arboviruses. The SARS-CoV-2 sequencing protocol involves whole genome sequencing using Oxford Nanopore and Illumina platforms, with associated bioinformatic, phylogenetic and statistical analytical pipelines. 
Type Of Material Technology assay or reagent 
Year Produced 2022 
Provided To Others? Yes  
Impact The serological assay will allow the characterisation of SARS-CoV-2 from vaccine induced and natural infections, thereby facilitating vaccine break-out, efficacy and other investigations. The ongoing sequencing has identified variants of concern and been used to characterise transmission patterns, thereby informing infection control decision making. 
 
Title Serological marker panel 
Description A serological marker panel consisting of 15 targets, including specific targets for adenoviruses, delta, and omicron SARS-CoV-2 variants. 
Type Of Material Technology assay or reagent 
Year Produced 2022 
Provided To Others? No  
Impact The panel can and has been been used to differentiate vaccine responses and natural COVID infections. 
 
Title SARS-CoV-2 sequencing database and informatics tools 
Description This is a set of informatic tools for the integrated analysis of SARS-CoV-2 sequencing, immunological, geo-temporal, and protein analysis. It is linked to a SARS-CoV-2 sequence database. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact It has facilitated the analysis of serological targets that may be robust post-vaccine roll-out. 
URL http://genomics.lshtm.ac.uk
 
Title Serological dataset 
Description Generation of serological data across a marker panel of 15 targets for >1000 individuals. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? No  
Impact Insights into the effectiveness of the Thailand vaccine roll-out and extent of protective immunity. 
 
Description Philippines Department of Health - COVID-19 genomics and serology 
Organisation Government of the Republic of the Philippines
Department Research Institute for Tropical Medicine (RITM) Phillippines
Country Philippines 
Sector Public 
PI Contribution Protocols for serology and genome sequencing. Bioinformatic and statistical pipelines to analyse the resulting data.
Collaborator Contribution Sample collection and processing.
Impact The collection of COVID-19 samples.
Start Year 2020
 
Description Thailand Ministry of Public Health - COVID-19 genomics and serology 
Organisation Ministry of Public Health
Country Thailand 
Sector Public 
PI Contribution Protocols for serology and genome sequencing. Bioinformatic and statistical pipelines to analyse the resulting data.
Collaborator Contribution Sample collection and processing.
Impact The collection of COVID-19 samples.
Start Year 2020
 
Description Training in genomic and serological laboratory methods 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Expert training in laboratory methods at the Thailand study site, thereby building and strengthening capacity in COVID-19 investigations.
Year(s) Of Engagement Activity 2022
 
Description Training in serological and genomic methods 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Training activities in serology and genomics in May and July 2022 in Thailand by the LSHTM team, followed travel to the UK for advanced training in July 2023.
Year(s) Of Engagement Activity 2022