Pre-existing cross-reactive antibodies to the SARS CoV-2 spike in sera from subjects in developing countries

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Principal Investigator: JAMES L ARTHOS
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2023
Award: $109,700
Funding agency: National Institute of Allergy and Infectious Diseases

Intranasal administration led to rapid lung alveolar macrophage uptake, pulmonary vascular leakage, and neutrophil recruitment and damage. Exposure to the spike protein enhanced neutrophil NETosis and augmented human macrophage TNF- and IL-6 production. Human and murine immune cells employed C-type lectin receptors and Siglecs to help capture the spike protein. This study highlights the potential toxicity of the SARS-CoV-2 Spike protein for mammalian cells and illustrates the central role for alveolar macrophages in pathogenic protein uptake.

We obtained serum samples from US, Thailand, Uganda, through collaborators under existing IRB approved protocols. In Thailand we will have access to samples from all age groups, including children. Each of these countries has experienced the Covid19 pandemic in a different way. Different variants were involved, providing us the opportunity to examine the potential of pre-existing antibodies to promote the emergence of a new variant. By evaluating both SARS CoV-2 binding and neutralization of pre- Covid19 sera we should be able to gain insight regarding the potential of pre-existing antibody responses to 1) impact the levels of infection in a given region and 2) impose immune pressure on emerging variants.

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