The Impact of Prior Immunity on B Cell Responses to Viral Antigens Eileen C Goodwin

Format:

Book

Thesis/Dissertation

Author/Creator:

Goodwin, Eileen C., author.

Contributor:

University of Pennsylvania. Immunology., degree granting institution.

Language:

English

Subjects (All):

Immunology.

Virology.

Microbiology.

0982.

0720.

0410.

Local Subjects:

Immunology.

Virology.

Microbiology.

0982.

0720.

0410.

Physical Description:

1 electronic resource (119 pages)

Contained In:

Dissertations Abstracts International 86-07B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2024

Language Note:

English

Summary:

Viral pathogens can evolve to evade antibody responses and permit re-infection, requiring this immunity to be updated. However, re-exposure tends to boost memory-derived antibody responses instead of inducing de novo responses to novel features of the current pathogen. To examine the contribution of circulating antibody to this phenomenon, we profiled the effects of a passively-transferred anti-hemagglutinin (HA) monoclonal antibody on the B cell response to influenza virions in mice. This antibody inhibited de novo HA-specific antibodies, plasmablasts, germinal center B cells, and memory B cells, while responses to other viral antigens were uninhibited. The inhibitory potency of the antibody varied across the HA head domain, with stronger inhibition of de novo responses to sites closest to the mAb binding site. These results suggest that circulating antibody inhibits de novo B cell responses in an antigen-specific manner, and that a monospecific antibody is sufficient to inhibit the majority of the B cell response to HA. Given the powerful influence of immune memory on de novo responses, we analyzed human serum samples collected at the beginning of the COVID-19 pandemic for evidence of whether immune memory to other betacoronaviruses impacted the resulting SARS-CoV-2 antibody response and clinical outcomes of infection. We identified cross-reactive antibodies in a fraction of SARS-CoV-2-naive serum samples, but the presence of these antibodies was not associated with protection from infection. Although few people had cross-reactive serum antibodies prior to infection, most hospitalized patients showed an increase in antibodies to a seasonally-circulating betacoronavirus during their SARS-CoV-2 infection, suggesting most people have cross-reactive antibodies that can be recalled by SARS-CoV-2 antigen. The boost of these antibodies was not associated with either better or worse infection outcome. Later research revealed that these recalled antibodies bound poorly to SARS-CoV-2 antigen, and that SARS-CoV-2 specific, de novo antibody responses occurred alongside this recall. Taken together, these studies show both the great potential of antibodies to inhibit de novo B cell responses and their limitations

Notes:

Source: Dissertations Abstracts International, Volume: 86-07, Section: B.

Advisors: Hensley, Scott E.; Eisenlohr, Laurence C. Committee members: Allman, David M.; Hunter, Christopher A.; Luning Prak, Eline T.; Yewdell, Jonathan W.

Ph.D. University of Pennsylvania 2024

Local Notes:

School code: 0175

ISBN:

9798302185730

Access Restriction:

Restricted for use by site license