Strain- and vaccine-specific effects of serum antibodies in the protection of intestinal SARS-CoV-2 infection Article Swipe
Michelle D. Cherne
,
Deann T. Snyder
,
Barkan Sidar
,
Karlin Blackwell
,
Brittany R. Jenkins
,
Sha Huang
,
Thomas A. Sebrell
,
Jodi F. Hedges
,
Jason R. Spence
,
Connie B. Chang
,
James N. Wilking
,
Seth T. Walk
,
Mark A. Jutila
,
Emma K. Loveday
,
Diane Bimczok
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.03.24.25324570
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.03.24.25324570
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a public health challenge worldwide. The gastrointestinal tract has emerged as an important site of infection and has been implicated as a reservoir for long-term infection, particularly for post-acute COVID-19 syndrome. However, whether vaccine-induced systemic antibodies can prevent intestinal infection with SARS-CoV-2 is unclear. Compared to Vero cells commonly used to assess SARS-CoV-2 neutralization, the intestinal epithelium has a functional interferon response and expresses higher levels of ACE2, enzymes, and antibody-binding Fc receptors that may impact SARS-CoV-2 immune elimination. Methods We evaluated the potential of antibodies from both naturally infected and vaccinated human subjects to inhibit SARS-CoV-2 infection of the intestinal epithelium. Serum samples were collected from human volunteers who had undergone natural infection with SARS-CoV-2 in 2020 (n=5) or who had received the Pfizer BNT162b2 COVID-19 vaccine (n=13). Banked sera collected in 2016 served as negative controls (n=2). SARS-CoV-2 (WA01, Delta or Omicron) was pre-treated with sera and then used to infect iPSC-derived human intestinal organoids (HIO) or Caco-2 colonic epithelial cells, and SARS-CoV-2 infection was quantified by plaque assay, PCR, or immunofluorescence (IF) after 48-96 h. Results Both HIOs and Caco-2 cells supported robust infection with SARS-CoV-2. In HIOs, pretreatment of SARS-CoV-2 with a high titer post-vaccine serum completely blocked replication of WA01. Similarly, sera from both naturally infected donors collected in 2020 and sera from individuals who had received a BNT162b2 vaccine significantly inhibited replication of the WA01 strain in Caco-2 cells. In contrast, none of the sera significantly inhibited infection with the Delta variant of SARS-CoV-2. For Omicron, only sera from individuals who had received an Omicron-based vaccine significantly inhibited infection with SARS-CoV-2 in the plaque assay. Across all virus types, sera from individuals who had received Omicron-based BNT162b2 boosters were the most effective at reducing infection in Caco-2 cells. Conclusion Our results suggest that vaccine-induced antibody responses to SARS-CoV-2 are protective in the gut. Our study also supports previous reports indicating that SARS-CoV-2 vaccines need to be adapted to circulating virus strains to convey full protection from infection.
Related Topics
Concepts
Vero cell
Antibody
Virology
Immune system
Intestinal epithelium
Immunology
Neutralization
Biology
Titer
Immunofluorescence
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus
Neutralizing antibody
Medicine
Epithelium
Virus
Coronavirus disease 2019 (COVID-19)
Disease
Infectious disease (medical specialty)
Pathology
Genetics
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.03.24.25324570
- OA Status
- green
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4408987180
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4408987180Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2025.03.24.25324570Digital Object Identifier
- Title
-
Strain- and vaccine-specific effects of serum antibodies in the protection of intestinal SARS-CoV-2 infectionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-03-28Full publication date if available
- Authors
-
Michelle D. Cherne, Deann T. Snyder, Barkan Sidar, Karlin Blackwell, Brittany R. Jenkins, Sha Huang, Thomas A. Sebrell, Jodi F. Hedges, Jason R. Spence, Connie B. Chang, James N. Wilking, Seth T. Walk, Mark A. Jutila, Emma K. Loveday, Diane BimczokList of authors in order
- Landing page
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https://doi.org/10.1101/2025.03.24.25324570Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1101/2025.03.24.25324570Direct OA link when available
- Concepts
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Vero cell, Antibody, Virology, Immune system, Intestinal epithelium, Immunology, Neutralization, Biology, Titer, Immunofluorescence, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus, Neutralizing antibody, Medicine, Epithelium, Virus, Coronavirus disease 2019 (COVID-19), Disease, Infectious disease (medical specialty), Pathology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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63Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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