Research

14 pages, 1031 KiB

Open AccessArticle

Crossroads between Autoimmunity and COVID-19 in Lung Transplant Recipients

by Madhusudhanan Narasimhan, Alagarraju Muthukumar, Kavithalakshmi Sataranatarajan, Lenin Mahimainathan, Luke Mahan, Irina Timofte, Srinivas Bollineni, John Joerns, Song Zhang, April Gorman, Amit Banga, Manish Mohanka, Fernando Torres, Adrian Lawrence, Mohanakumar Thalachallour and Vaidehi Kaza

Viruses 2023, 15(10), 2045; https://doi.org/10.3390/v15102045 - 03 Oct 2023

Viewed by 1023

Abstract

The presence of a certain group of auto-antibodies (AAbs) is known to correlate with the severity of COVID-19. It is, however, unknown if such AAbs are prevalent and impact COVID-19-related outcomes in lung transplant recipients (LTRs) who are immunosuppressed. We performed a retrospective [...] Read more.

The presence of a certain group of auto-antibodies (AAbs) is known to correlate with the severity of COVID-19. It is, however, unknown if such AAbs are prevalent and impact COVID-19-related outcomes in lung transplant recipients (LTRs) who are immunosuppressed. We performed a retrospective study of LTRs with COVID-19 and analyzed samples before and after COVID-19 for IgG AAbs. AAbs analysis was carried out using autoimmune and coronavirus microarray and the resulting cross-sectional differences in Ab-scores and clinical variables were analyzed using Fischer’s Exact test for categorical variables and a paired t-test for continuous variables. Linear regression was used to analyze the differences in Ab-scores and COVID-19 severity. LTRs with non-severe [NS gp (n = 10)], and severe [S gp (n = 8)] COVID-19 disease were included. Ferritin and acute respiratory failure were higher in the S group (p = 0.03; p < 0.0001). Among the AAbs analyzed, interferon-related AAbs (IFN-alpha2, IFN-beta, IFN lamba, IFN-epsilon), eight interleukin-related AAbs, and several tissue-related AAbs were also found to be changed significantly from pre- to post-COVID-19 (p < 0.05). IFN-lambda (p = 0.03) and IL-22 (p = 0.002) were significantly associated with COVID-19 severity and remained significant in linear regression analysis while controlling for other variables. AAbs are common in LTRs, and certain groups of antibodies are particularly enhanced in LTRs with severe COVID-19. Preliminary observations of this study need to be confirmed by a larger sample size. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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15 pages, 2813 KiB

Open AccessArticle

Humoral Responses Elicited after a Fifth Dose of SARS-CoV-2 mRNA Bivalent Vaccine

by Alexandra Tauzin, Guillaume Beaudoin-Bussières, Mehdi Benlarbi, Manon Nayrac, Yuxia Bo, Gabrielle Gendron-Lepage, Halima Medjahed, Josée Perreault, Laurie Gokool, Pascale Arlotto, Chantal Morrisseau, Cécile Tremblay, Daniel E. Kaufmann, Valérie Martel-Laferrière, Inès Levade, Marceline Côté, Renée Bazin and Andrés Finzi

Viruses 2023, 15(9), 1926; https://doi.org/10.3390/v15091926 - 15 Sep 2023

Cited by 2 | Viewed by 1307

Abstract

While an important part of the world’s population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize several Omicron subvariants, including BQ.1.1, [...] Read more.

While an important part of the world’s population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize several Omicron subvariants, including BQ.1.1, XBB, XBB.1.5, FD.1.1, and CH.1.1. However, Fc-effector functions remain strong and stable over time against new variants, which may partially explain why vaccines continue to be effective. We also observe that donors who have been recently infected have stronger antibody functional activities, including neutralization and Fc-effector functions, supporting the observations that hybrid immunity leads to better humoral responses. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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17 pages, 2507 KiB

Open AccessArticle

BA.1/BA.5 Immunogenicity, Reactogenicity, and Disease Activity after COVID-19 Vaccination in Patients with ANCA-Associated Vasculitis: A Prospective Observational Cohort Study

by Claudius Speer, Maximilian Töllner, Louise Benning, Marie Bartenschlager, Heeyoung Kim, Christian Nusshag, Florian Kälble, Marvin Reineke, Paula Reichel, Paul Schnitzler, Martin Zeier, Christian Morath, Wilhelm Schmitt, Raoul Bergner, Ralf Bartenschlager, Hanns-Martin Lorenz and Matthias Schaier

Viruses 2023, 15(8), 1778; https://doi.org/10.3390/v15081778 - 21 Aug 2023

Viewed by 1187

Abstract

Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective [...] Read more.

Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective studies that have focused exclusively on AAV patients are lacking. In addition, there are safety concerns regarding the use of highly immunogenic mRNA vaccines in autoimmune diseases, and further studies investigating reactogenicity are urgently needed. In this prospective observational cohort study, we performed a detailed characterization of neutralizing antibody responses against omicron subtypes and provided a longitudinal assessment of vaccine reactogenicity and AAV disease activity. Different vaccine doses were generally well tolerated and no AAV relapses occurred during follow-up. AAV patients had significantly lower anti-S1 IgG and surrogate-neutralizing antibodies after first, second, and third vaccine doses as compared to healthy controls, respectively. Live-virus neutralization assays against omicron subtypes BA.1 and BA.5 revealed that previous SARS-CoV-2 vaccines result in an inadequate neutralizing immune response in immunocompromised AAV patients. These data demonstrate that new vaccination strategies including adapted mRNA vaccines against epitopes of emerging variants are needed to help protect highly vulnerable individuals such as AAV patients. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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12 pages, 1340 KiB

Open AccessArticle

BNT162b2 Elicited an Efficient Cell-Mediated Response against SARS-CoV-2 in Kidney Transplant Recipients and Common Variable Immunodeficiency Patients

by Evelina La Civita, Carla Zannella, Stefano Brusa, Paolo Romano, Elisa Schettino, Fabrizio Salemi, Rosa Carrano, Luca Gentile, Alessandra Punziano, Gianluca Lagnese, Giuseppe Spadaro, Gianluigi Franci, Massimiliano Galdiero, Daniela Terracciano, Giuseppe Portella and Stefania Loffredo

Viruses 2023, 15(8), 1659; https://doi.org/10.3390/v15081659 - 30 Jul 2023

Cited by 4 | Viewed by 1301

Abstract

SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test [...] Read more.

SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test humoral and cell-mediated response after three doses of BNT162b vaccine in two cohorts of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients compared to healthy donors. We enrolled 10 healthy controls (HCs), 19 CVID patients and 17 KTR patients. HC BNT162b third dose had successfully mounted humoral immune response. A positive correlation between Anti-Spike Trimeric IgG concentration and neutralizing antibody titer was also observed. CVID and KTR groups showed a lower humoral immune response compared to HCs. IFN-γ release induced by epitopes of the Spike protein in stimulated CD4⁺ and CD8⁺ T cells was similar among vaccinated HC, CVID and KTR. Patients vaccinated and infected showed a more efficient humoral and cell-mediated response compared to only vaccinated patients. In conclusion, CVID and KTR patients had an efficient cell-mediated but not humoral response to SARS-CoV-2 vaccine, suggesting that the evaluation of T cell responses could be a more sensitive marker of immunization in these subjects. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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15 pages, 3481 KiB

Open AccessArticle

Reduced Humoral and Cellular Immune Response to Primary COVID-19 mRNA Vaccination in Kidney Transplanted Children Aged 5–11 Years

by Jasmin K. Lalia, Raphael Schild, Marc Lütgehetmann, Gabor A. Dunay, Tilmann Kallinich, Robin Kobbe, Mona Massoud, Jun Oh, Leonora Pietzsch, Ulf Schulze-Sturm, Catharina Schuetz, Freya Sibbertsen, Fabian Speth, Sebastian Thieme, Mario Witkowski, Reinhard Berner, Ania C. Muntau, Søren W. Gersting, Nicole Toepfner, Julia Pagel and Kevin Paul Show full author list Hide full author list

Viruses 2023, 15(7), 1553; https://doi.org/10.3390/v15071553 - 14 Jul 2023

Cited by 1 | Viewed by 1281

Abstract

The situation of limited data concerning the response to COVID-19 mRNA vaccinations in immunocom-promised children hinders evidence-based recommendations. This prospective observational study investigated humoral and T cell responses after primary BNT162b2 vaccination in secondary immunocompromised and healthy children aged 5–11 years. Participants were [...] Read more.

The situation of limited data concerning the response to COVID-19 mRNA vaccinations in immunocom-promised children hinders evidence-based recommendations. This prospective observational study investigated humoral and T cell responses after primary BNT162b2 vaccination in secondary immunocompromised and healthy children aged 5–11 years. Participants were categorized as: children after kidney transplantation (KTx, n = 9), proteinuric glomerulonephritis (GN, n = 4) and healthy children (controls, n = 8). Expression of activation-induced markers and cytokine secretion were determined to quantify the T cell response from PBMCs stimulated with peptide pools covering the spike glycoprotein of SARS-CoV-2 Wuhan Hu-1 and Omicron BA.5. Antibodies against SARS-CoV-2 spike receptor-binding domain were quantified in serum. Seroconversion was detected in 56% of KTx patients and in 100% of the GN patients and controls. Titer levels were significantly higher in GN patients and controls than in KTx patients. In Ktx patients, the humoral response increased after a third immunization. No differences in the frequency of antigen-specific CD4+ and CD8+ T cells between all groups were observed. T cells showed a predominant anti-viral capacity in their secreted cytokines; however, this capacity was reduced in KTx patients. This study provides missing evidence concerning the humoral and T cell response in immunocompromised children after COVID-19 vaccination. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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10 pages, 1262 KiB

Open AccessArticle

Comparison of Immune Responses between Inactivated and mRNA SARS-CoV-2 Vaccines Used for a Booster Dose in Mice

by Ning Luan, Han Cao, Yunfei Wang, Kangyang Lin, Jingping Hu and Cunbao Liu

Viruses 2023, 15(6), 1351; https://doi.org/10.3390/v15061351 - 11 Jun 2023

Viewed by 1244

Abstract

A large amount of real-world data suggests that the emergence of variants of concern (VOCs) has brought new challenges to the fight against SARS-CoV-2 because the immune protection elicited by the existing coronavirus disease 2019 (COVID-19) vaccines was weakened. In response to the [...] Read more.

A large amount of real-world data suggests that the emergence of variants of concern (VOCs) has brought new challenges to the fight against SARS-CoV-2 because the immune protection elicited by the existing coronavirus disease 2019 (COVID-19) vaccines was weakened. In response to the VOCs, it is necessary to advocate for the administration of booster vaccine doses to extend the effectiveness of vaccines and enhance neutralization titers. In this study, the immune effects of mRNA vaccines based on the WT (prototypic strain) and omicron (B1.1.529) strains for use as booster vaccines were investigated in mice. It was determined that with two-dose inactivated vaccine priming, boosting with mRNA vaccines could elevate IgG titers, enhance cell-mediated immunity, and provide immune protection against the corresponding variants, but cross-protection against distinct strains was inferior. This study comprehensively describes the differences in the mice boosted with mRNA vaccines based on the WT strain and the omicron strain, a harmful VOC that has resulted in a sharp rise in the number of infections, and reveals the most efficacious vaccination strategy against omicron and future SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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19 pages, 1900 KiB

Open AccessArticle

Integration of Cellular and Humoral Immune Responses as an Immunomonitoring Tool for SARS-CoV-2 Vaccination in Healthy and Fragile Subjects

by Giulia Brisotto, Marcella Montico, Matteo Turetta, Stefania Zanussi, Maria Rita Cozzi, Roberto Vettori, Romina Boschian Boschin, Lorenzo Vinante, Fabio Matrone, Alberto Revelant, Elisa Palazzari, Roberto Innocente, Giuseppe Fanetti, Lorenzo Gerratana, Mattia Garutti, Camilla Lisanti, Silvia Bolzonello, Milena Sabrina Nicoloso, Agostino Steffan and Elena Muraro

Viruses 2023, 15(6), 1276; https://doi.org/10.3390/v15061276 - 30 May 2023

Viewed by 1626

Abstract

Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and [...] Read more.

Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy. We found that higher titers of antibodies were associated with a higher probability of positive cellular immunity and that this greater immune response was correlated with an increased number of vaccination side effects. Moreover, active T-cell immunity after vaccination was associated with reduced antibody decay. The vaccine-induced cellular immunity appeared more likely in healthy subjects rather than in cancer patients. Lastly, after boosting, we observed a cellular immune conversion in 20% of subjects, and a strong correlation between pre- and post-boosting IFN-γ levels, while antibody levels did not display a similar association. Finally, our data suggested that integrating humoral and cellular immune responses could allow the identification of SARS-CoV-2 vaccine responders and that T-cell responses seem more stable over time compared to antibodies, especially in cancer patients. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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Review

Jump to: Research, Other

18 pages, 1867 KiB

Open AccessReview

Advances of Reverse Vaccinology for mRNA Vaccine Design against SARS-CoV-2: A Review of Methods and Tools

by Maria Karolaynne da Silva, Daniel Melo de Oliveira Campos, Shopnil Akash, Shahina Akter, Leow Chiuan Yee, Umberto Laino Fulco and Jonas Ivan Nobre Oliveira

Viruses 2023, 15(10), 2130; https://doi.org/10.3390/v15102130 - 21 Oct 2023

Cited by 1 | Viewed by 1728

Abstract

mRNA vaccines are a new class of vaccine that can induce potent and specific immune responses against various pathogens. However, the design of mRNA vaccines requires the identification and optimization of suitable antigens, which can be challenging and time consuming. Reverse vaccinology is [...] Read more.

mRNA vaccines are a new class of vaccine that can induce potent and specific immune responses against various pathogens. However, the design of mRNA vaccines requires the identification and optimization of suitable antigens, which can be challenging and time consuming. Reverse vaccinology is a computational approach that can accelerate the discovery and development of mRNA vaccines by using genomic and proteomic data of the target pathogen. In this article, we review the advances of reverse vaccinology for mRNA vaccine design against SARS-CoV-2, the causative agent of COVID-19. We describe the steps of reverse vaccinology and compare the in silico tools used by different studies to design mRNA vaccines against SARS-CoV-2. We also discuss the challenges and limitations of reverse vaccinology and suggest future directions for its improvement. We conclude that reverse vaccinology is a promising and powerful approach to designing mRNA vaccines against SARS-CoV-2 and other emerging pathogens. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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19 pages, 1558 KiB

Open AccessReview

Vaccines’ New Era-RNA Vaccine

by Wenshuo Zhou, Linglei Jiang, Shimiao Liao, Feifei Wu, Guohuan Yang, Li Hou, Lan Liu, Xinping Pan, William Jia and Yuntao Zhang

Viruses 2023, 15(8), 1760; https://doi.org/10.3390/v15081760 - 18 Aug 2023

Cited by 6 | Viewed by 2989

Abstract

RNA vaccines, including conventional messenger RNA (mRNA) vaccines, circular RNA (circRNA) vaccines, and self-amplifying RNA (saRNA) vaccines, have ushered in a promising future and revolutionized vaccine development. The success of mRNA vaccines in combating the COVID-19 pandemic caused by the SARS-CoV-2 virus that [...] Read more.

RNA vaccines, including conventional messenger RNA (mRNA) vaccines, circular RNA (circRNA) vaccines, and self-amplifying RNA (saRNA) vaccines, have ushered in a promising future and revolutionized vaccine development. The success of mRNA vaccines in combating the COVID-19 pandemic caused by the SARS-CoV-2 virus that emerged in 2019 has highlighted the potential of RNA vaccines. These vaccines possess several advantages, such as high efficacy, adaptability, simplicity in antigen design, and the ability to induce both humoral and cellular immunity. They also offer rapid and cost-effective manufacturing, flexibility to target emerging or mutant pathogens and a potential approach for clearing immunotolerant microbes by targeting bacterial or parasitic survival mechanisms. The self-adjuvant effect of mRNA-lipid nanoparticle (LNP) formulations or circular RNA further enhances the potential of RNA vaccines. However, some challenges need to be addressed. These include the technology’s immaturity, high research expenses, limited duration of antibody response, mRNA instability, low efficiency of circRNA cyclization, and the production of double-stranded RNA as a side product. These factors hinder the widespread adoption and utilization of RNA vaccines, particularly in developing countries. This review provides a comprehensive overview of mRNA, circRNA, and saRNA vaccines for infectious diseases while also discussing their development, current applications, and challenges. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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17 pages, 3259 KiB

Open AccessReview

The Potential Role of SARS-CoV-2 Infection and Vaccines in Multiple Sclerosis Onset and Reactivation: A Case Series and Literature Review

by Eleonora Tavazzi, Anna Pichiecchio, Elena Colombo, Eleonora Rigoni, Carlo Asteggiano, Elisa Vegezzi, Francesco Masi, Giacomo Greco, Stefano Bastianello and Roberto Bergamaschi

Viruses 2023, 15(7), 1569; https://doi.org/10.3390/v15071569 - 18 Jul 2023

Cited by 3 | Viewed by 2983

Abstract

The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected [...] Read more.

The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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16 pages, 333 KiB

Open AccessReview

Research Advances on the Stability of mRNA Vaccines

by Feiran Cheng, Yiping Wang, Yu Bai, Zhenglun Liang, Qunying Mao, Dong Liu, Xing Wu and Miao Xu

Viruses 2023, 15(3), 668; https://doi.org/10.3390/v15030668 - 02 Mar 2023

Cited by 16 | Viewed by 6013

Abstract

Compared to other vaccines, the inherent properties of messenger RNA (mRNA) vaccines and their interaction with lipid nanoparticles make them considerably unstable throughout their life cycles, impacting their effectiveness and global accessibility. It is imperative to improve mRNA vaccine stability and investigate the [...] Read more.

Compared to other vaccines, the inherent properties of messenger RNA (mRNA) vaccines and their interaction with lipid nanoparticles make them considerably unstable throughout their life cycles, impacting their effectiveness and global accessibility. It is imperative to improve mRNA vaccine stability and investigate the factors influencing stability. Since mRNA structure, excipients, lipid nanoparticle (LNP) delivery systems, and manufacturing processes are the primary factors affecting mRNA vaccine stability, optimizing mRNA structure and screening excipients can effectively improve mRNA vaccine stability. Moreover, improving manufacturing processes could also prepare thermally stable mRNA vaccines with safety and efficacy. Here, we review the regulatory guidance associated with mRNA vaccine stability, summarize key factors affecting mRNA vaccine stability, and propose a possible research path to improve mRNA vaccine stability. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

Other

Jump to: Research, Review

11 pages, 1632 KiB

Open AccessBrief Report

B and T Cell Responses to SARS-CoV-2 Vaccination in Kidney and Liver Transplant Recipients with and without Previous COVID-19

by Christina Watschinger, Gerald Stampfel, Andreas Zollner, Anna M. Hoog, Annika Rössler, Silvia Reiter, Kristina Dax, Janine Kimpel, Herbert Tilg, Marlies Antlanger, Elisabeth Schwaiger and Alexander R. Moschen

Viruses 2024, 16(1), 1; https://doi.org/10.3390/v16010001 - 19 Dec 2023

Cited by 1 | Viewed by 947

Abstract

(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney organ recipients at our centre. (2) Methods: 23 liver and 45 kidney (14 thereof combined kidney/pancreas) transplanted patients were [...] Read more.

(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney organ recipients at our centre. (2) Methods: 23 liver and 45 kidney (14 thereof combined kidney/pancreas) transplanted patients were vaccinated with two doses of BNT162b2 followed by a booster dose of mRNA-1273 in 28 non-responders 4 months thereafter. Anti-SARS-CoV-2-Ig was measured by specific ELISA and virus neutralisation assay; T cell responses were measured by a spike protein-specific IFN-γ release assay. (3) Results: Compared to controls, B and T cell responses were weak in transplant recipients, particularly in those without prior exposure to SARS-CoV-2. Within this group, only 15% after the first and 58.3% after the second vaccination achieved seroconversion. A total of 14 out of 28 vaccination non-responders achieved a seroconversion after a third dose. Vaccination side effects were more frequent in healthy controls. The use of mycophenolate was associated with reduced anti-SARS-CoV-2-Ig production. (4) Conclusions: Our data confirm that vaccination responses are insufficient after standard vaccination in liver and kidney transplant recipients and are affected to a variable degree by specific immunosuppressants, particularly mycophenolate. Monitoring vaccination success and re-vaccinating those who are unresponsive seems prudent to achieve sufficient titres. Overall, prospective large-scale, multinational, multicentre studies or high-quality meta-analyses will be needed to generate personalised vaccination strategies in order to achieve protective immunity in high-risk, hard-to-immunize populations. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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10 pages, 1788 KiB

Open AccessBrief Report

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac

by Çiğdem Erol, Zeynep Ece Kuloğlu, Bircan Kayaaslan, Gülen Esken, Adalet Altunsoy, Tayfun Barlas, Güle Çınar, İmran Hasanoğlu, Ebru Oruç, Said İncir, Alpay Azap, Gülten Korkmaz, Dilara Turan Gökçe, Onur Elvan Kırımker, Ezgi Coşkun Yenigün, Erkan Ölçücüoğlu, Ebru Ayvazoğlu Soy, Süleyman Çetinkünar, Özlem Kurt Azap, Füsun Can and Mehmet Haberal Show full author list Hide full author list

Viruses 2023, 15(7), 1534; https://doi.org/10.3390/v15071534 - 12 Jul 2023

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Abstract

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT [...] Read more.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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15 pages, 1413 KiB

Open AccessBrief Report

Humoral and T Cell Immune Responses against SARS-CoV-2 after Primary and Homologous or Heterologous Booster Vaccinations and Breakthrough Infection: A Longitudinal Cohort Study in Malaysia

by Jolene Yin Ling Fu, Muhammad Harith Pukhari, Maria Kahar Bador, I-Ching Sam and Yoke Fun Chan

Viruses 2023, 15(4), 844; https://doi.org/10.3390/v15040844 - 25 Mar 2023

Cited by 3 | Viewed by 1928

Abstract

Vaccine efficacy against SARS-CoV-2 could be compromised by the emergence of SARS-CoV-2 variants and it is important to study how it impacts the booster vaccination regime. We investigated the humoral and T cell responses longitudinally in vaccinated uninfected (n = 25) and [...] Read more.

Vaccine efficacy against SARS-CoV-2 could be compromised by the emergence of SARS-CoV-2 variants and it is important to study how it impacts the booster vaccination regime. We investigated the humoral and T cell responses longitudinally in vaccinated uninfected (n = 25) and post-COVID-19 individuals (n = 8), and those who had received a BNT162b2 booster following complete two-doses regimes of either BNT162b2 (homologous) (n = 14) or ChAdOx1-S (heterologous) (n = 15) vaccines, by means of a SARS-CoV-2 pseudovirus neutralization test and QuantiFERON SARS-CoV-2 assay. Vaccinated post-COVID-19 individuals showed higher neutralizing antibodies with longer durability against SARS-CoV-2 wild type (WT) and Omicron spikes, but demonstrated similar declining T cell responses compared to the uninfected vaccinated. Two doses of BNT162b2 induced higher neutralizing antibodies against WT and T cell responses than ChAdOx1-S for six months. The BNT162b2 booster confers a greater humoral response against WT, but a similar cross-neutralizing antibody against Omicron and T cell responses in the homologous booster group compared to the heterologous booster group. Breakthrough infection in the homologous booster group (n = 11) significantly increased the neutralizing antibody, but T cell responses remained low. Our data may impact government public health policy regarding the administration of mix-and-match vaccines, where both vaccination regimes can be employed should there be shortages of certain vaccines. Full article

(This article belongs to the Special Issue SARS-CoV-2 and mRNA Vaccines)

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