Immune imprinting shapes antibody responses to influenza viruses and sars-cov-2 Shuk Hang Li

Format:

Book

Thesis/Dissertation

Author/Creator:

Li, Shuk Hang, author.

Contributor:

University of Pennsylvania. Cell and Molecular Biology., degree granting institution.

Language:

English

Subjects (All):

Virology.

Public health.

Immunology.

0720.

0982.

0573.

Local Subjects:

Virology.

Public health.

Immunology.

0720.

0982.

0573.

Genre:

Academic theses

Physical Description:

1 online resource (218 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

Respiratory viruses present an ongoing challenge as they continuously evolve, accumulating mutations that allow escape from existing immunity. Simultaneously, immune memory from past exposures profoundly shapes how individuals respond to antigenically drifted variants. This dissertation explores how prior immune exposures influence antibody responses to evolving respiratory viruses. First, we demonstrate that childhood exposures create lasting immune imprints that elicit cross-subtype antibodies. We isolated monoclonal antibodies after influenza vaccination and identified cross-subtype antibodies that targeted the head domain of influenza hemagglutinin that is conserved between contemporary strains and strains that circulated in early childhood of the vaccinees. We show that antibodies targeting this epitope can be elicited in ferrets sequentially exposed to influenza viruses of different subtypes, and H1N1 has recently acquired a substitution on the epitope that abrogated binding of these antibodies. Similarly, using human serological cohorts, we demonstrate that early exposures mounted cross-reactive antibodies that protect against a different subtype. We show that older individuals, who were likely immunologically imprinted in childhood with group 1 viruses (H1N1 or H2N2), have higher levels of antibodies that cross-react to H5N1 compared to younger individuals. We also show that H5-reactive antibodies were boosted across all age groups but with the greatest increase found in children. Next, we show that SARS-CoV-2 infection and mRNA vaccination induce antibodies that are cross-reactive to other coronaviruses. However, infections elicited more original antigenic sin-like antibodies that bind efficiently to the spike of common seasonal coronaviruses but poorly to the SARS- CoV-2 spike whereas mRNA vaccination elicited antibodies that cross-react more efficiently to the SARS- CoV-2 spike. As SARS-CoV-2 continues to evolve, we determine how exposures to antigenically distant variants shape antibody responses. We demonstrate that repeat exposures primarily lead to back-boosting of antibodies that targeted epitopes conserved between the variant and the ancestral spike. Nonetheless, individuals with low baseline immunity can mount some variant-specific responses, particularly against more antigenically distant strains. These findings highlight that immune history is a major determinant of antibody responses to antigenically advanced variants, providing crucial insights for improving vaccine strain selection, vaccine effectiveness, and pandemic preparedness

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Hensley, Scott E. Committee members: Bates, Paul F.; Jurado, Kellie Ann; Shaw, George M.; Weissman, Drew

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247983330

Access Restriction:

Restricted for use by site license