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Related Concept Videos

Vaccinations01:51

Vaccinations

Overview
Cross-reactivity00:42

Cross-reactivity

Overview
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Vaccines01:21

Vaccines

Vaccines are among the most effective tools in preventive medicine, designed to prepare the immune system to recognize and combat infectious agents. By introducing antigens—substances that the immune system identifies as foreign—vaccines stimulate an adaptive immune response that leads to immunological memory. This immunological memory enables the body to mount a faster and more effective response upon future exposures to the actual pathogen.Vaccines can be categorized based on the type of...
Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial exposure to a...

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Updated: Jul 4, 2026

Determination of Vaccine Immunogenicity Using Bovine Monocyte-Derived Dendritic Cells
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Published on: May 19, 2023

COVID-19 Vaccine Reactogenicity Marks an Innate Inflammatory Response Associated With HLA Variation and Enhanced

Jill Hollenbach1, Anshika Srivastava2,3,4, Demetra Chatzileontiadou2,3,5

  • 1Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.

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Human leukocyte antigen (HLA) variations significantly influence COVID-19 vaccine side effects and protection. Specific HLA types like HLA-A*03:01 are linked to increased reactogenicity and fewer infections, suggesting side effects may indicate immune activation.

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Area of Science:

  • Immunogenetics
  • Vaccinology
  • Infectious Disease Epidemiology

Background:

  • COVID-19 vaccines are crucial for pandemic control, but systemic side effects can cause hesitancy.
  • The link between human leukocyte antigen (HLA) variations, vaccine reactogenicity, and protection is not fully understood.
  • Investigating immunogenetic determinants of vaccine response is essential for understanding vaccine efficacy and safety.

Purpose of the Study:

  • To investigate the genetic and immunological determinants of vaccine reactogenicity and its association with protection against SARS-CoV-2.
  • To explore the role of HLA variation in systemic side effects following COVID-19 vaccination.
  • To elucidate the mechanisms underlying vaccine reactogenicity and its relationship with immune response.

Main Methods:

  • Analysis of a large cohort (50,535 individuals) with deep genotyping and phenotyping, replicated in an independent cohort (4,575 individuals).
  • Statistical association testing for HLA alleles and vaccine reactogenicity, including COVID-19 and influenza vaccines.
  • Functional immunological analyses, including cytokine profiling and assessment of T-cell activation in response to vaccination.

Main Results:

  • A strong association was confirmed between HLA-A*03:01 and increased systemic side effects post-COVID-19 vaccination (OR = 1.36).
  • HLA-B*08:01 was linked to reduced reactogenicity across COVID-19 and influenza vaccines, suggesting separable genetic influences.
  • Stronger vaccine side effects correlated with reduced infection risk and milder disease, independent of HLA genotype, and were linked to early monocyte inflammatory cytokine responses, not enhanced antigen-specific T-cell activation.

Conclusions:

  • Vaccine reactogenicity results from an interplay between antigen-specific immunogenetic factors and innate inflammatory responses.
  • Transient vaccine side effects may serve as a clinically observable correlate of protective immune activation.
  • Understanding these mechanisms can help address vaccine hesitancy and optimize vaccine strategies.