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Principal Investigator: Patrick Duffy
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $13,666
Funding agency: National Institute of Allergy and Infectious Diseases
In July 2020, we commenced a community COVID-19 seroprevalence study at existing clinical trials sites in Mali. This study is a Public Health Surveillance Activity in collaboration with the Ministry of Health in Mali to describe the sero-epidemiology of COVID-19 in urban and rural populations. Using the demographic and clinical information collected from participants, we will describe the age-stratified seroprevalence and fraction of asymptomatic/pauci-symptomatic cases to help understand the penetration of SARS-CoV-2 into the community. Additional exploratory objectives to understand viral carriage, locally circulating variants, and improve direct virus detection at study sites have been added to help enhance local capacity for Public Health surveillance and possible future clinical trials. Separately, we have leveraged our in-house vaccine platforms to develop COVID-19 vaccine candidates that may be suitable for use in low/middle income countries like Mali.
We report progress from the following publication in FY2024:
Krajacich BJ, Samaké D, Dao A, Diallo M, Sanogo ZL, Yaro AS, Zeguime A, Poudiougo J, Cissé K, Traoré M, Assitoun AD, Faiman R, Zaidi I, Woodford J, Duffy PE, Lehmann T. Tracking SARS-CoV-2 seropositivity in rural communities using blood-fed mosquitoes: a proof of concept study. 2023. Frontiers in Epidemiology. Dec 13; doi:10.3389/fepid.2023.1243691
This study evaluated the use of naturally blood-fed mosquitoes to detect human anti-SARS-CoV-2 antibodies in laboratory and field settings across five locations in Mali. IgG antibodies to multiple SARS-CoV-2 antigens were detected in mosquito bloodmeals up to 10 hours after feeding, with a mean sensitivity of 0.92 and specificity of 0.98. This indicates blood-fed mosquitoes collected indoors in the early morning are viable samples for analysis. Reactivity to SARS-CoV-2 antigens increased during the pandemic. Crude seropositivity from mosquito-sampled blood was 6.3% in October-November 2020 and rose to 25.1% by February 2021, with the most urban site reaching 46.7%, aligning with venous blood-based sero-surveillance estimates. Using mosquito bloodmeals for sero-surveillance is feasible and effective for monitoring human diseases in areas with common human-biting mosquitoes. This method offers a cost-effective, non-invasive alternative for large-scale disease surveillance.
To summarize the results of the vaccine development activities undertaken during this project:
Activity 1: Production of various constructs of Omicron RBD:
Receptor binding domains of three different Omicron variants were obtained from NCI
Activity 2: Synthesis and characterization of RBD conjugates of Omicron RBDs with EcoCRM carrier:
RBD conjugates of three different Omicron variants with EcoCRM were synthesized and characterized.
Activity 3: Evaluate immunogenicity and functional activity of conjugates in mice:
Evaluation of Omicron conjugates could not be carried out since the funding for COVID research was terminated during the project period.
Activity 4: Evaluate selected conjugate vaccines in non-human primates:
Conjugate of SARS-CoV-2 receptor binding domain (RBD) with a carrier protein EcoCRM was synthesized and its immunogenicity was evaluated in Rhesus Macaque. This conjugate was initially evaluated in mouse studies and shown to induce strong antibody response with high virus neutralization activity against different variants. (Results from the mouse study was published in 2022). The Rhesus study evaluated two different doses of the RBD conjugate adjuvanted with clinical adjuvant AS01 and compared it with Pfizer/BioNTech mRNA vaccine. Antibody response induced by the conjugates were very similar or greater than that from the mRNA vaccine. Similarly, virus neutralization activity of the immune sera from the conjugates were also very similar to that of mRNA. Both mRNA and conjugates induced similar IgG subclass profile at different time points up to 280 days, the duration of the study. Overall, the conjugate performed as well as the mRNA in all the immunological assays carried out so far. Additional parameters are being assessed and a manuscript is under preparation describing the results.
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