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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.
True
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.
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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?
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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.
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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 ___.
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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.
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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:
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What is a significant effect of hybrid immunity on neutralizing antibodies?
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Memory B cells do not persist after infection.
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What are breakthrough infections?
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Hybrid immunity is generated through __________ before or after vaccination.
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Match the following terms with their descriptions:
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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?
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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?
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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:
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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.
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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.
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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.
