SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and...

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Immune responses to viral infections are influenced by prior exposure to related strains, a process termed imprinting.
• Widespread SARS-CoV-2 (COVID-19) imprinting has occurred due to early pandemic infections and vaccinations.
• Imprinting shapes the antibody response, often boosting cross-reactive antibodies from the initial exposure.

Purpose of the Study:

• To compare the neutralizing antibody specificities in individuals imprinted by early SARS-CoV-2 strains versus infants with primary infection by a recent XBB* variant.
• To investigate how different SARS-CoV-2 exposure histories affect antibody targeting of the spike protein.

Main Methods:

• Utilized pseudovirus-based deep mutational scanning to assess antibody neutralization.
• Measured neutralization by serum antibodies from adults/children imprinted by original vaccines and infants with primary XBB* infection.
• Compared antibody responses before and after secondary XBB* spike exposure via vaccination in infants.

Main Results:

• Imprinted individuals' serum antibodies primarily targeted the spike receptor-binding domain (RBD).
• Infants with primary XBB* infection showed neutralizing activity mainly targeting the spike N-terminal domain (NTD).
• Infant vaccination boosted neutralizing activity towards the RBD, but targeted different sites than imprinted adults.

Conclusions:

• Distinct SARS-CoV-2 exposure histories lead to significant differences in neutralizing antibody specificities.
• Antibody responses in imprinted individuals and infants with primary infection show divergent targeting of spike protein domains.
• These differences in neutralization specificities may influence the future evolution of SARS-CoV-2.