Immune Correlates of Protection in Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Innate and Adaptive Immunity in Vaccination".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 24991

Special Issue Editor

Division of Drug and Vaccine Research, Guangzhou Laboratory, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510320, China
Interests: vaccine development; oncolytic viral therapy; virus–host interaction; innate immunity; viral entry

Special Issue Information

Dear Colleagues, 

Despite tremendous progress in the medical field, infectious diseases and cancers remain the chief culprit, undermining our quality of life. An inadequate understanding of immune responses during viral infections or tumorigenesis dramatically hampers the development of countermeasures. Moreover, a comprehensive characterization of immune correlates of protection will inform our fundamental understanding of pathogenesis and guide vaccine development. Previous vaccine efforts have underscored the crucial roles of both humoral and cellular immunity against viral pathogens and cancers. 

This Special Issue aims to enrich our current knowledge of immune responses, elicited naturally or by vaccination, and their contribution to protective efficacy. We cordially invite research articles and reviews that investigate branches of immunities. This covers but does not limit to innate immunity, T cell immunity, B cell immunity, humoral immunity, trained immunity and so forth. We hope that these highlights will inform superior next-generation vaccine design.

Dr. Jingyou Yu
Guest Editor

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Keywords

  • vaccine
  • humoral immunity
  • cellular immunity
  • innate immunity
  • infectious disease
  • virus
  • cancer

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Published Papers (11 papers)

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Research

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13 pages, 2253 KiB  
Article
Antibody Persistence and Risk of COVID-19 Infection: Insights from Modeling
by Laurent Coudeville, Eleine Konate, Tabassome Simon, Xavier de Lamballerie, Scott Patterson, Clotilde El Guerche-Séblain and Odile Launay
Vaccines 2024, 12(9), 1079; https://doi.org/10.3390/vaccines12091079 - 21 Sep 2024
Viewed by 959
Abstract
Background: In this post hoc exploratory study of the APHP-COVIBOOST trial (NCT05124171), we used statistical modeling to describe the evolution of neutralizing antibody (nAb) titers over time, asses its impact on SARS-CoV-2 infection, and explore potential differences between three booster vaccine formulations (D614, [...] Read more.
Background: In this post hoc exploratory study of the APHP-COVIBOOST trial (NCT05124171), we used statistical modeling to describe the evolution of neutralizing antibody (nAb) titers over time, asses its impact on SARS-CoV-2 infection, and explore potential differences between three booster vaccine formulations (D614, B.1.351, and BNT162b2). Methods: Antibody titers were measured for 208 adult participants at day 28, 3 months, and 6 months using a microneutralization assay against different Omicron subvariants. We developed four specific Bayesian statistical models based on a core model, accounting for vaccine-specific antibody decline, boosting of nAb for breakthrough infection, and risk of infection according to nAb levels. The model findings were cross-verified using another validated microneutralization assay. Results: The decrease in nAb titers was significantly lower for the B.1.351 vaccine than for the other booster formulations. An inverse relationship was found between risk of infection upon exposure and nAb levels. With Omicron BA.1 data, these results translated into a positive relative vaccine efficacy against any infection over 6 months for the B.1.351 vaccine compared to the BNT162b2 (31%) and D614 (21%) vaccines. Conclusions: Risk of infection decreased with increasing nAb titers for all vaccines. Statistical models predicted significantly better antibody persistence for the B.1.351 booster formulation compared to the other evaluated vaccines. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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10 pages, 221 KiB  
Article
Timing of Assessment of Humoral and Cell-Mediated Immunity after Influenza Vaccination
by Naruhito Otani, Kazuhiko Nakajima, Kumiko Yamada, Kaori Ishikawa, Kaoru Ichiki, Takashi Ueda, Yoshio Takesue, Takuma Yamamoto, Satoshi Higasa, Susumu Tanimura, Yuta Inai and Toshiomi Okuno
Vaccines 2024, 12(6), 584; https://doi.org/10.3390/vaccines12060584 - 27 May 2024
Viewed by 876
Abstract
Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing [...] Read more.
Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing of immunological assessments after vaccination using markers of humoral and cell-mediated immunity. In the 2018/2019 influenza season, blood was collected from 29 healthy adults before and after vaccination with a quadrivalent inactivated influenza vaccine, and we performed serial measurements of humoral immunity (hemagglutination inhibition [HAI] and neutralizing antibody [NT]) and cell-mediated immunity (interferon-gamma [IFN-γ]). The HAI and NT titers before and after vaccination were strongly correlated, but no correlation was observed between the markers of cell-mediated and humoral immunity. The geometric mean titer and geometric mean concentration of humoral and cellular immune markers increased within 2 weeks after vaccination and had already declined by 8 weeks. This study suggests that the optimal time to assess the immune response is 2 weeks after vaccination. Appropriately timed immunological assessments can help ensure that vaccination is effective. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
15 pages, 2711 KiB  
Article
Local Enrichment with Convergence of Enriched T-Cell Clones Are Hallmarks of Effective Peptide Vaccination against B16 Melanoma
by Anna Vyacheslavovna Izosimova, Alexandra Valerievna Shabalkina, Mikhail Yurevich Myshkin, Elizaveta Viktorovna Shurganova, Daria Sergeevna Myalik, Ekaterina Olegovna Ryzhichenko, Alina Faritovna Samitova, Ekaterina Vladimirovna Barsova, Irina Aleksandrovna Shagina, Olga Vladimirovna Britanova, Diana Vladimirovna Yuzhakova and George Vladimirovich Sharonov
Vaccines 2024, 12(4), 345; https://doi.org/10.3390/vaccines12040345 - 22 Mar 2024
Viewed by 1640
Abstract
Background: Some peptide anticancer vaccines elicit a strong T-cell memory response but fail to suppress tumor growth. To gain insight into tumor resistance, we compared two peptide vaccines, p20 and p30, against B16 melanoma, with both exhibiting good in vitro T-cell responses but [...] Read more.
Background: Some peptide anticancer vaccines elicit a strong T-cell memory response but fail to suppress tumor growth. To gain insight into tumor resistance, we compared two peptide vaccines, p20 and p30, against B16 melanoma, with both exhibiting good in vitro T-cell responses but different tumor suppression abilities. Methods: We compared activation markers and repertoires of T-lymphocytes from tumor-draining (dLN) and non-draining (ndLN) lymph nodes for the two peptide vaccines. Results: We showed that the p30 vaccine had better tumor control as opposed to p20. p20 vaccine induced better in vitro T-cell responsiveness but failed to suppress tumor growth. Efficient antitumor vaccination is associated with a higher clonality of cytotoxic T-cells (CTLs) in dLNs compared with ndLNs and the convergence of most of the enriched clones. With the inefficient p20 vaccine, the most expanded and converged were clones of the bystander T-cells without an LN preference. Conclusions: Here, we show that the clonality and convergence of the T-cell response are the hallmarks of efficient antitumor vaccination. The high individual and methodological dependencies of these parameters can be avoided by comparing dLNs and ndLNs. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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16 pages, 2211 KiB  
Article
A Recombinant Multivalent Vaccine (rCpa1) Induces Protection for C57BL/6 and HLA Transgenic Mice against Pulmonary Infection with Both Species of Coccidioides
by Althea Campuzano, Komali Devi Pentakota, Yu-Rou Liao, Hao Zhang, Nathan P. Wiederhold, Gary R. Ostroff and Chiung-Yu Hung
Vaccines 2024, 12(1), 67; https://doi.org/10.3390/vaccines12010067 - 9 Jan 2024
Cited by 4 | Viewed by 1878
Abstract
Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci), which have a 4–5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) [...] Read more.
Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci), which have a 4–5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from Cp isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1-based vaccine against both species of Coccidioides. DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of Cp and Ci, respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against five highly virulent isolates of Cp and Ci. There are total of seven amino acid substitutions in the rCpa1 antigen between Cp and Ci. Both C57BL/6 and HLA-DR4 mice that were vaccinated with an rCpa1 vaccine had a significant reduction of fungal burden and increased numbers of IFN-γ- and IL-17-producing CD4+ T cells in the first 2 weeks post challenge. These data suggest that rCpa1 has cross-protection activity against Cp and Ci pulmonary infection through activation of early Th1 and Th17 responses. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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16 pages, 3544 KiB  
Article
Development of A Standardized Opsonophagocytosis Killing Assay for Group B Streptococcus and Assessment in an Interlaboratory Study
by Stephanie Leung, Clare F. Collett, Lauren Allen, Suzanna Lim, Pete Maniatis, Shanna J. Bolcen, Bailey Alston, Palak Y. Patel, Gaurav Kwatra, Tom Hall, Stephen Thomas, Stephen Taylor, Kirsty Le Doare and Andrew Gorringe
Vaccines 2023, 11(11), 1703; https://doi.org/10.3390/vaccines11111703 - 9 Nov 2023
Viewed by 2605
Abstract
The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, [...] Read more.
The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65–3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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20 pages, 3561 KiB  
Article
In Silico Analyses, Experimental Verification and Application in DNA Vaccines of Ebolavirus GP-Derived pan-MHC-II-Restricted Epitopes
by Junqi Zhang, Baozeng Sun, Wenyang Shen, Zhenjie Wang, Yang Liu, Yubo Sun, Jiaxing Zhang, Ruibo Liu, Yongkai Wang, Tianyuan Bai, Zilu Ma, Cheng Luo, Xupeng Qiao, Xiyang Zhang, Shuya Yang, Yuanjie Sun, Dongbo Jiang and Kun Yang
Vaccines 2023, 11(10), 1620; https://doi.org/10.3390/vaccines11101620 - 20 Oct 2023
Cited by 2 | Viewed by 1989
Abstract
(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host [...] Read more.
(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host cells. DNA vaccines for EBOV are in development, but their effectiveness is unclear. The lack of immune characteristics resides in antigenic MHC class II reactivity. (2) Methods: We selected MHC-II molecules from four human leukocyte antigen II (HLA-II) superfamilies with 98% population coverage and eight mouse H2-I alleles. IEDB, NetMHCIIpan, SYFPEITHI, and Rankpep were used to screen MHC-II-restricted epitopes with high affinity for EBOV GP. Further immunogenicity and conservation analyses were performed using VaxiJen and BLASTp, respectively. EpiDock was used to simulate molecular docking. Cluster analysis and binding affinity analysis of EBOV GP epitopes and selected MHC-II molecules were performed using data from NetMHCIIpan. The selective GP epitopes were verified by the enzyme-linked immunospot (ELISpot) assay using splenocytes of BALB/c (H2d), C3H, and C57 mice after DNA vaccine pVAX-GPEBO immunization. Subsequently, BALB/c mice were immunized with Protein-GPEBO, plasmid pVAX-GPEBO, and pVAX-LAMP/GPEBO, which encoded EBOV GP. The dominant epitopes of BALB/c (H-2-I-AdEd genotype) mice were verified by the enzyme-linked immunospot (ELISpot) assay. It is also used to evaluate and explore the advantages of pVAX-LAMP/GPEBO and the reasons behind them. (3) Results: Thirty-one HLA-II-restricted and 68 H2-I-restricted selective epitopes were confirmed to have high affinity, immunogenicity, and conservation. Nineteen selective epitopes have cross-species reactivity with good performance in MHC-II molecular docking. The ELISpot results showed that pVAX-GPEBO could induce a cellular immune response to the synthesized selective peptides. The better immunoprotection of the DNA vaccines pVAX-LAMP/GPEBO coincides with the enhancement of the MHC class II response. (4) Conclusions: Promising MHC-II-restricted candidate epitopes of EBOV GP were identified in humans and mice, which is of great significance for the development and evaluation of Ebola vaccines. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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14 pages, 3543 KiB  
Article
Influenza H7N9 Virus Hemagglutinin with T169A Mutation Possesses Enhanced Thermostability and Provides Effective Immune Protection against Lethal H7N9 Virus Challenge in Chickens
by Taoran Chen, Dexin Kong, Xiaolong Hu, Yinze Gao, Shaorong Lin, Ming Liao and Huiying Fan
Vaccines 2023, 11(8), 1318; https://doi.org/10.3390/vaccines11081318 - 2 Aug 2023
Cited by 1 | Viewed by 1739
Abstract
H7N9 avian influenza virus (AIV) has caused huge losses in the poultry industry and impacted human public health security, and still poses a potential threat. Currently, immune prevention and control of avian influenza relies on traditional inactivated vaccines; however, they have some limitations [...] Read more.
H7N9 avian influenza virus (AIV) has caused huge losses in the poultry industry and impacted human public health security, and still poses a potential threat. Currently, immune prevention and control of avian influenza relies on traditional inactivated vaccines; however, they have some limitations and genetically engineered avian influenza subunit vaccines may be potential candidate vaccines. In this study, a T169A mutation in the HA protein derived from H7N9 AIV A/Chicken/Guangdong/16876 (H7N9-16876) was generated using the baculovirus expression system (BVES). The results showed that the mutant (HAm) had significantly increased thermostability compared with the wild-type HA protein (HA-WT). Importantly, immunizing chickens with HAm combined with ISA 71VG elicited higher cross-reactive hemagglutination inhibition (HI) antibody responses and cytokine (IFN-γ and IL-4) secretion. After a lethal challenge with heterologous H7N9 AIV, the vaccine conferred chickens with 100% (10/10) clinical protection and effectively inhibited viral shedding, with 90% (9/10) of the chickens showing no virus shedding. The thermostability of HAm may represent an advantage in practical vaccine manufacture and application. In general, the HAm generated in this study represents a promising subunit vaccine candidate for the prevention and control of H7N9 avian influenza. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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Review

Jump to: Research

16 pages, 1305 KiB  
Review
Intranasal Immunization of Pneumococcal pep27 Mutant Attenuates Allergic and Inflammatory Diseases by Upregulating Skin and Mucosal Tregs
by Hamid Iqbal and Dong-Kwon Rhee
Vaccines 2024, 12(7), 737; https://doi.org/10.3390/vaccines12070737 - 3 Jul 2024
Viewed by 1179
Abstract
Conventional immunization methods such as intramuscular injections lack effective mucosal protection against pathogens that enter through the mucosal surfaces. Moreover, conventional therapy often leads to adverse events and compromised immunity, followed by complicated outcomes, leading to the need to switch to other options. [...] Read more.
Conventional immunization methods such as intramuscular injections lack effective mucosal protection against pathogens that enter through the mucosal surfaces. Moreover, conventional therapy often leads to adverse events and compromised immunity, followed by complicated outcomes, leading to the need to switch to other options. Thus, a need to develop safe and effective treatment with long-term beneficial outcomes to reduce the risk of relapse is mandatory. Mucosal vaccines administered across mucosal surfaces, such as the respiratory or intestinal mucosa, to prompt robust localized and systemic immune responses to prevent the public from acquiring pathogenic diseases. Mucosal immunity contains a unique immune cell milieu that selectively identify pathogens and limits the transmission and progression of mucosal diseases, such as allergic dermatitis and inflammatory bowel disease (IBD). It also offers protection from localized infection at the site of entry, enables the clearance of pathogens on mucosal surfaces, and leads to the induction of long-term immunity with the ability to shape regulatory responses. Regulatory T (Treg) cells have been a promising strategy to suppress mucosal diseases. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Nasal immunization protects mucosal surfaces, but nasal antigen presentation appears to entail the need for an adjuvant to stimulate immunogenicity. Here, a novel method is developed to induce Tregs via intranasal immunization without an adjuvant to potentially overcome allergic diseases and gut and lung inflammation using lung–gut axis communication in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies on Treg resilience through clinical translational studies on dietary changes. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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40 pages, 2342 KiB  
Review
Nanoparticles and Antiviral Vaccines
by Sen Liu, Meilin Hu, Xiaoqing Liu, Xingyu Liu, Tao Chen, Yiqiang Zhu, Taizhen Liang, Shiqi Xiao, Peiwen Li and Xiancai Ma
Vaccines 2024, 12(1), 30; https://doi.org/10.3390/vaccines12010030 - 27 Dec 2023
Cited by 7 | Viewed by 4027
Abstract
Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to [...] Read more.
Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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13 pages, 1512 KiB  
Review
The Application of Mesenchymal Stem Cells in Future Vaccine Synthesis
by Rui Zhang, Xingxiang Duan, Ye Liu, Jia Xu, Abdullkhaleg Ali Ghaleb Al-bashari, Peng Ye, Qingsong Ye and Yan He
Vaccines 2023, 11(11), 1631; https://doi.org/10.3390/vaccines11111631 - 24 Oct 2023
Cited by 1 | Viewed by 1849
Abstract
Vaccines have significant potential in treating and/or preventing diseases, yet there remain challenges in developing effective vaccines against some diseases, such as AIDS and certain tumors. Mesenchymal stem cells (MSCs), a subset of cells with low immunogenicity, high proliferation potential, and an abundant [...] Read more.
Vaccines have significant potential in treating and/or preventing diseases, yet there remain challenges in developing effective vaccines against some diseases, such as AIDS and certain tumors. Mesenchymal stem cells (MSCs), a subset of cells with low immunogenicity, high proliferation potential, and an abundant source of extracellular vesicles (EVs), represent one of the novel and promising vaccine platforms. This review describes the unique features and potential mechanisms of MSCs as a novel vaccine platform. We also cover aspects such as the safety and stability of MSCs that warrant future in-depth studies. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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11 pages, 919 KiB  
Review
Immune Imprinting and Implications for COVID-19
by Zhiqian Zhou, Julia Barrett and Xuan He
Vaccines 2023, 11(4), 875; https://doi.org/10.3390/vaccines11040875 - 20 Apr 2023
Cited by 19 | Viewed by 5171
Abstract
Immunological memory is the key source of protective immunity against pathogens. At the current stage of the COVID-19 pandemic, heterologous combinations of exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, the downside of memory, might limit [...] Read more.
Immunological memory is the key source of protective immunity against pathogens. At the current stage of the COVID-19 pandemic, heterologous combinations of exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, the downside of memory, might limit the generation of de novo immune response against variant infection or the response to the next-generation vaccines. Here, we review mechanistic basis of immune imprinting by focusing on B cell immunobiology and discuss the extent to which immune imprinting is harmful, as well as its effect on SARS-CoV-2 infection and vaccination. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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