Podcast
Questions and Answers
Which of the following vaccines is NOT mentioned as a response to the COVID-19 pandemic?
Which of the following vaccines is NOT mentioned as a response to the COVID-19 pandemic?
The primary correlation of protection against SARS-CoV-2 infection is the presence of neutralizing antibodies in the serum after vaccination.
The primary correlation of protection against SARS-CoV-2 infection is the presence of neutralizing antibodies in the serum after vaccination.
True
What is the most efficient method for detecting antibodies following vaccination?
What is the most efficient method for detecting antibodies following vaccination?
ELISA screening
The _____ levels six months after the second vaccine dose are similar to levels after the first vaccine dose.
The _____ levels six months after the second vaccine dose are similar to levels after the first vaccine dose.
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Match the vaccine with its manufacturer:
Match the vaccine with its manufacturer:
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Which method is used to test for the presence of virally specific CD4+ and CD8+ T cells?
Which method is used to test for the presence of virally specific CD4+ and CD8+ T cells?
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Which vaccine induced stronger initial antibody responses compared to the other?
Which vaccine induced stronger initial antibody responses compared to the other?
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The antibody titers from the mRNA vaccines remained stable up to 8 months after vaccination.
The antibody titers from the mRNA vaccines remained stable up to 8 months after vaccination.
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What type of T cells showed a very strong response after administration of the BNT162b2 Pfizer vaccine?
What type of T cells showed a very strong response after administration of the BNT162b2 Pfizer vaccine?
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The spike-specific T cell response induced by vaccination with the BNT162b2 Pfizer vaccine resulted in a significant increase in the production of ___.
The spike-specific T cell response induced by vaccination with the BNT162b2 Pfizer vaccine resulted in a significant increase in the production of ___.
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How did the antibody responses of the Adenovirus vaccine compare to the mRNA vaccines over 8 months?
How did the antibody responses of the Adenovirus vaccine compare to the mRNA vaccines over 8 months?
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CD8+ T cells showed higher levels of response compared to CD4+ T cells after administration of the second vaccine.
CD8+ T cells showed higher levels of response compared to CD4+ T cells after administration of the second vaccine.
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What happens to gamma interferon levels after 6 months of receiving the second vaccination with the BNT162b2 Pfizer vaccine?
What happens to gamma interferon levels after 6 months of receiving the second vaccination with the BNT162b2 Pfizer vaccine?
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Match the vaccine with its characteristic antibody response:
Match the vaccine with its characteristic antibody response:
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What is a significant effect of hybrid immunity on neutralizing antibodies?
What is a significant effect of hybrid immunity on neutralizing antibodies?
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Memory B cells do not persist after infection.
Memory B cells do not persist after infection.
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What are breakthrough infections?
What are breakthrough infections?
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Hybrid immunity is generated through __________ before or after vaccination.
Hybrid immunity is generated through __________ before or after vaccination.
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Match the following terms with their descriptions:
Match the following terms with their descriptions:
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What characteristic is enhanced in B memory cells after hybrid immunity?
What characteristic is enhanced in B memory cells after hybrid immunity?
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Which SARS-CoV-2 variant was identified first among the following options?
Which SARS-CoV-2 variant was identified first among the following options?
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CD4+ and CD8+ T cell responses are unaffected by mutant variants.
CD4+ and CD8+ T cell responses are unaffected by mutant variants.
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What is the time frame during which the Mu (B.1.621) and Delta (B.1.617.2) variants were observed?
What is the time frame during which the Mu (B.1.621) and Delta (B.1.617.2) variants were observed?
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Hybrid immunity refers to the immune response in individuals who have had a natural infection prior to __________.
Hybrid immunity refers to the immune response in individuals who have had a natural infection prior to __________.
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Match the SARS-CoV-2 variants with their identification period:
Match the SARS-CoV-2 variants with their identification period:
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Which T cell subtype is primarily associated with recognizing diverse Spike epitopes?
Which T cell subtype is primarily associated with recognizing diverse Spike epitopes?
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Breakthrough infections occur only in vaccinated individuals without previous infections.
Breakthrough infections occur only in vaccinated individuals without previous infections.
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What percentage of individuals showed CD8+ memory T cell responses after the second vaccine dose?
What percentage of individuals showed CD8+ memory T cell responses after the second vaccine dose?
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The protective T cell response is maintained for _______ months after vaccination.
The protective T cell response is maintained for _______ months after vaccination.
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Which Spike variant was recognized by both CD4+ and CD8+ T cells?
Which Spike variant was recognized by both CD4+ and CD8+ T cells?
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Study Notes
SARS-CoV-2 Vaccines and Immunity
- Three vaccines that were developed in response to the COVID-19 pandemic are:
- BNT162b2 (Pfizer/BioNTech)
- mRNA-1273 (Moderna)
- Ad26.COV2.S (Johnson & Johnson)
Measuring Immune Response After Vaccination
- The presence of neutralizing antibodies in the serum is the primary indicator of protection against SARS-CoV-2 infection following vaccination.
- ELISA screening is the most efficient way to detect antibodies after vaccination.
- The presence of virus-specific CD4+ and CD8+ T cells is more challenging to study.
- Flow cytometry is used to detect the presence of virally specific CD4+ and CD8+ T cells.
Antibody Responses to SARS-CoV-2 Induced by Vaccination
- Both Moderna and Pfizer vaccines create strong antibody responses.
- Antibody levels peak one week after the second dose and decline slightly after six months.
- Moderna recipients have slightly higher antibody titers than Pfizer recipients.
- Individuals with prior COVID infection and individuals who were vaccinated had a good antibody response to both Pfizer and Moderna vaccines.
- The Adenovirus (Ad26.COV2.S) vaccine induces lower initial antibody responses compared to mRNA vaccines but remains relatively stable for eight months.
Spike-Specific T Cell Responses Induced by Vaccination
- Vaccination with the Pfizer vaccine induces strong CD4+ T cell responses with a slight decline after six months.
- CD8+ T cell levels are elevated but not as high as CD4+ after the second dose of the vaccine.
- T cell levels are significantly elevated compared to individuals who are not vaccinated.
- Gamma interferon (IFN-γ), a major cytokine produced by Th1 cells, is produced in high amounts by CD4+ and CD8+ T cells following vaccination.
- Despite a slight decrease, IFN-γ levels remain elevated after six months of receiving the second vaccination.
SARS-CoV-2 Variants of Concern
- Numerous SARS-CoV-2 variants of concern (VOC) have emerged with varying degrees of transmissibility and resistance to existing immunity.
- Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) VOCs emerged between late 2020 and May 2021.
- Mu (B.1.621) and Delta (B.1.617.2) emerged between May and November 2021.
- Omicron (B.1.1.529) emerged in November 2021 and is highly transmissible even in populations with high levels of immunity.
SARS-CoV-2 Vaccination and Variants
- CD4+ and CD8+ T cells are unaffected by mutant variants of the virus because the protective T cell response is not solely specific to the Spike-receptor binding domain.
- Vaccination leads to the development of Spike-specific CD4+ memory T cells detected in nearly 100% of individuals weeks and six months after the second dose.
- Similar responses are observed for mRNA and adenoviral vector vaccines.
- CD8+ memory T cells are detected in 70-90% of individuals after the second dose and 45-65% at six months.
- Both mRNA and adenoviral vector vaccines elicit similar responses.
- Both CD4+ and CD8+ memory T cells recognize diverse Spike epitopes and viral variants, including Omicron.
T Cell Responses to Viral Variants
- T cells from individuals vaccinated with mRNA or adenovirus vaccines show recognition of SARS-CoV-2 variants, including Omicron.
- Most T cell epitopes are conserved across different variants.
- Memory T cell responses are maintained for 6-7 months after vaccination.
- The repertoire of T cell epitopes reveals 11 Spike epitopes recognized by CD4+ T cells and 10 Spike epitopes recognized by CD8+ T cells.
Hybrid Immunity
- A decrease in neutralizing antibodies can be attributed to the emergence of viral variants.
- Breakthrough infections occur due to the emergence of viral variants.
- Hybrid immunity refers to the immune response observed in individuals who have experienced a natural infection prior to vaccination or in vaccinated individuals who have had a breakthrough infection.
- Extensive studies examine T and B cell immunity in vaccinated individuals with breakthrough infections and responses to viral variants.
Hybrid Immunity: CD4+, CD8+, and B Memory Cells
- Individuals with hybrid immunity have increased CD4+ and CD8+ memory T cell responses compared to natural infection or vaccination alone.
- These individuals have circulating CD4+ and CD8+ memory T cells, and tissue-resident memory cells are generated.
- B memory cells specific to the Receptor Binding Domain (RBD) have more somatic hypermutation and affinity maturation compared to vaccination alone.
Antibody Response in Hybrid Immunity
- Neutralizing antibody titers improve in individuals with hybrid immunity.
- The breadth of neutralization of SARS-CoV-2 variants increases.
- Antibody titers are 5 to 17 times higher after six months compared to vaccination alone.
Hybrid Immunity: Breakthrough Infection and Vaccination
- Antibodies from individuals with breakthrough infections and vaccination after natural infection broadly neutralize SARS-CoV-2.
- SARS-CoV-2 infection before or after vaccination significantly boosts the neutralizing antibody response compared to two doses of vaccine.
- Vaccination after recovery from natural SARS-CoV-2 infection ("hybrid immunity") substantially increases the potency and breadth of the humoral response to SARS-CoV-2.
- This hybrid immunity elicits significantly higher amounts of cross-variant neutralizing antibodies compared to vaccination of naive individuals alone.
- Strong immunity from hybrid immunity might be due to higher clonal turnover of B cells and greater somatic hypermutation in SARS-CoV-2 recovered individuals compared to naturally infected or naive vaccinated individuals.
Memory B Cells
- Memory B cells persist after infection, evolve continuously, and mature by acquiring somatic mutations in their variable-region genes to improve affinity through an ongoing germinal center response.
- Understanding how mRNA vaccination influences the Memory B cell pool shaped by prior exposure to SARS-CoV-2 and its capacity to neutralize variants is crucial.
- It is important to investigate differences and evolution of Memory B cells from naive vaccinees compared to SARS-CoV-2-recovered individuals.
- Vaccination boosts the expansion of high-affinity Receptor Binding Domain-specific memory B cells in COVID-19-recovered individuals, eliciting a strong serum antibody response that includes cross-neutralizing antibodies to variants of concern.
- Vaccination of SARS-CoV-2-naive individuals induces low neutralizing antibodies to variants, and the maturation of RBD-specific memory B cells is less pronounced.
Strong Immunity in Hybrid Immunity
- Strong immunity against SARS-CoV-2 in vaccinated individuals with prior natural infection is due to:
- Receptor Binding Domain-specific memory B cells
- Neutralizing antibodies to viral variants
Advantages of Hybrid Immunity Over Vaccination
- Individuals with hybrid immunity have a broader repertoire of virus-specific antibodies.
- They exhibit robust T cell responses, including T cells specific to not only the Spike protein but also other SARS-CoV-2 proteins.
- CD4+ T cells in individuals with hybrid immunity are characterized by a functional profile of interferon gamma (IFN-γ) and low IL-10 production.
SARS-CoV-2 Antibody Detection in Patients
- The detection of SARS-CoV-2-specific IgM and IgG in patients is the basis for disease diagnosis, utilized in conjunction with RT-PCR-based tests.
- Reports indicate that patients with severe disease often have an increased IgG response and higher titers of total antibodies, which are associated with worse outcomes.
- High levels of antibody detection may indicate that the FC portion is binding to antibodies that have receptors specific to the FC region, leading to enhanced viral replication.
- If an antibody binds to a virus, a cell may become engulfed, facilitating viral replication.
- This phenomenon refers to immune backfire or antibody-dependent enhancement (ADE).
Antibody-Dependent Enhancement
- Antibody-dependent enhancement (ADE) is a process where a virus leverages antibodies to aid infection.
- Non-neutralizing antibodies can bind to macrophages, facilitating the virus's entry into those cells and potentially accelerating viral replication.
Conclusion
- Both natural infection, vaccination, and breakthrough infections elicit adaptive T and B cell responses to SARS-CoV-2.
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Description
This quiz explores the various SARS-CoV-2 vaccines developed during the COVID-19 pandemic, including their mechanisms and effectiveness. It also covers how to measure the immune response post-vaccination and the antibody responses induced by these vaccines.
