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SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 21441

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Dr. Zoltan Vajo

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Department of Family Medicine, Semmelweis University Medical School, 1125 Budapest, Hungary
Interests: influenza; vaccines; serology; clinical trials
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Dear Colleagues,

During the assessment and licensing of novel vaccines, and in the post-licensure follow up, it is critical to have reliable immunogenicity-testing methods that relate well to protection. The need for reliable immunogenicity criteria became apparent in preparation for the potential pandemic threat posed by influenza A H5N1 in 2006, when great intra- and interlaboratory variations were seen for hemagglutinin inhibition and microneutralization tests, and the need for a centralized standard was acknowledged by the WHO and NIBSC.

In the case of SARS-CoV-2, this remains a critical issue, as many different antibody tests have been developed urgently, but with unknown correlation to real-world protection. Therefore, collaboration among different laboratories and health authorities is essential to establish standards and to reduce interlaboratory variations, and to establish immunogenicity correlates that can be used for licensing as well as patient care. In this Special Issue, we seek papers discussing the development of reliable immunogenicity tests that correlate with the real-world protection of SARS-CoV-2 and other novel vaccines.

Sub-topics: antibody levels; cellular immunity; correlates of protection; rapid vs laboratory antibody kits; the role of ELISA

Dr. Zoltan Vajo
Guest Editor

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Keywords

SARS-CoV-2
serology
cellular immune response
protection
vaccines

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Published Papers (11 papers)

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Editorial

Jump to: Research, Other

2 pages, 159 KiB

Open AccessEditorial

Extinction of the Influenza B Yamagata Line during the COVID Pandemic—Implications for Vaccine Composition

by Zoltan Vajo and Peter Torzsa

Viruses 2022, 14(8), 1745; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081745 - 09 Aug 2022

Cited by 3 | Viewed by 2097

Abstract

Vaccination remains the most effective way to mitigate the enormous burden of influenza on the health care system [...] Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

Research

Jump to: Editorial, Other

14 pages, 2053 KiB

Open AccessArticle

Real-World Effectiveness of COVID-19 Vaccine and Identification of SARS-CoV-2 Variants among People Living with HIV on Highly Active Antiretroviral Therapy in Central Kerala of India—An Ambi-Directional Cohort Study

by Joe Thomas, Priyanka Rajmohan, Ponnu Jose, Radhika Kannan, Rosmi Jose, Unnikrishnan Uttumadathil Gopinathan, Lucy Raphael, Nithya M. Baiju, Swathi Krishna, Teny Attokaran, Jubina Bency A. T, Aiswarya Venugopal, Soorya Sheela, Akhila Kallempadam, Lee Jose, Susheela J. Innah, Pulikkottil Raphael Varghese and Alex George

Viruses 2023, 15(11), 2187; https://0-doi-org.brum.beds.ac.uk/10.3390/v15112187 - 30 Oct 2023

Cited by 1 | Viewed by 1392

Abstract

Background: Vaccine effectiveness for first-generation coronavirus disease (COVID-19) vaccines among People Living with HIV (PLHIV) in India remains unexplored. This study entails the estimation of the real-world effectiveness of COVID-19 vaccines (AZD1222/Covishield, BBV152/Covaxin) among PLHIV and the identification of variants of SARS-CoV-2 among those infected with COVID-19. Methods: An ambi-directional cohort study was conducted among 925 PLHIV above 18 years of age in two districts of central Kerala, India, from February 2022 to March 2023. Selected PLHIV were recruited as Participant Liaison Officers (PLOs) for the follow-up on the study participants. At enrolment, basic details, baseline CD4 count, and a Nasopharyngeal (NP) swab for RT-PCR were collected. In the follow-up phase, NP swabs were collected from subjects with COVID-19 symptoms. Positive subjects had a CD4 count and genomic sequencing performed. Results: The mean age of the participants was 46.93 ± 11.00 years. The majority, 819 (93.6%), of participants had received at least one dose of any vaccine, while 56 (6.4%) were unvaccinated. A total of 649 (79.24%) participants were vaccinated with Covishield and 169 (20.63%) with Covaxin. In the vaccinated group, 158 (19.3%) reported COVID-19 infection. Vaccine Effectiveness (VE) for one dose of any vaccine was 43.2% (95% CI: 11.8–64.5), p = 0.015. The effectiveness of full vaccination with Covishied was 63.8% (95% CI: 39.3–79.2), p < 0.001, and Covaxin was 73.4% (95% CI: 44.3–87.3). VE was highest, at 60.7% (95% CI: 23.6–81.3), when the two doses of the vaccine were given at an interval of less than 6 weeks. Participants with a baseline CD4 count > 350 had greater protection from COVID-19, at 53.4% (95% CI: 19.6–75.3) p = 0.004. The incident cases were sub-variants of Omicron (BA.2, BA.2.38, BA.2.10). Conclusions: Full vaccination with Covishield and Covaxin was effective against COVID-19 infection among PLHIV on treatment; albeit, that of Covaxin was higher. A gap of 4 to 6 weeks between the two doses of COVID-19 vaccine was found to have higher VE among PLHIV. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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15 pages, 3327 KiB

Open AccessArticle

Cluster Analysis Identifies Distinct Patterns of T-Cell and Humoral Immune Responses Evolution Following a Third Dose of SARS-CoV-2 Vaccine in People Living with HIV

by Majdouline El Moussaoui, Salomé Desmecht, Nicolas Lambert, Nathalie Maes, Joachim Braghini, Nicole Marechal, Céline Quintana, Karine Briquet, Stéphanie Gofflot, Françoise Toussaint, Marie-Pierre Hayette, Pieter Vermeersch, Laurence Lutteri, Céline Grégoire, Yves Beguin, Souad Rahmouni, Michel Moutschen, Daniel Desmecht and Gilles Darcis

Viruses 2023, 15(7), 1435; https://0-doi-org.brum.beds.ac.uk/10.3390/v15071435 - 26 Jun 2023

Cited by 1 | Viewed by 1144

Abstract

(1) Background: Many vaccines require higher, additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Despite their potential risk of severe coronavirus disease 2019, immunological data remain sparse, and a clear consensus for the best booster strategy is lacking. (2) Methods: Using the data obtained from our previous study assessing prospective T-cell and humoral immune responses before and after administration of a third dose of SARS-CoV-2 vaccine, we assessed the correlations between immune parameters reflecting humoral and cellular immune responses. We further aimed at identifying distinct clusters of patients with similar patterns of immune response evolution to determine how these relate to demographic and clinical factors. (3) Results: Among 80 PLWH and 51 healthcare workers (HCWs) enrolled in the study, cluster analysis identified four distinct patterns of evolution characterised by specific immune patterns and clinical factors. We observed that immune responses appeared to be less robust in cluster A, whose individuals were mostly PLWH who had never been infected with SARS-CoV-2. Cluster C, whose individuals showed a particularly drastic increase in markers of humoral immune response following the third dose of vaccine, was mainly composed of female participants who experienced SARS-CoV-2. Regarding the correlation study, although we observed a strong positive correlation between markers mirroring humoral immune response, markers of T-cell response following vaccination correlated only in a lesser extent with markers of humoral immunity. This suggests that neutralising antibody titers alone are not always a reliable reflection of the magnitude of the whole immune response. (4) Conclusions: Our findings show heterogeneity in immune responses among SARS-CoV-2 vaccinated PLWH. Specific subgroups could therefore benefit from distinct immunization strategies. Prior or breakthrough natural infection enhances the activity of vaccines and must be taken into account for informing global vaccine strategies among PLWH, even those with a viro-immunologically controlled infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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10 pages, 1373 KiB

Open AccessCommunication

Detection of IgA and IgG Antibodies against the Structural Proteins of SARS-CoV-2 in Breast Milk and Serum Samples Derived from Breastfeeding Mothers

by Karen Cortés-Sarabia, Vianey Guzman-Silva, Karla Montserrat Martinez-Pacheco, Jesús Alberto Meza-Hernández, Víctor Manuel Luna-Pineda, Marco Antonio Leyva-Vázquez, Amalia Vences-Velázquez, Fredy Omar Beltrán-Anaya, Oscar Del Moral-Hernández and Berenice Illades-Aguiar

Viruses 2023, 15(4), 966; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040966 - 14 Apr 2023

Cited by 1 | Viewed by 2241

Abstract

Background: COVID-19 vaccination or natural infection is associated with the development of immunity. The search of IgA and IgG antibodies against all the structural proteins (spike, nucleocapsid, membrane, and envelope) of SARS-CoV-2 in breastfeeding mothers is associated with immunity that can help the newborn avoid development of the infection. Methods: In this study, we analyzed 30 breastfeeding women that provided samples of breast milk and serum and evaluated the presence of IgA, total IgG, and subclasses against the structural proteins of SARS-CoV-2. Results: We reported a high seroprevalence to IgA (76.67–100%) and negativity to IgG against all analyzed proteins in breast milk. Seroprevalence in serum samples was around 10–36.67% to IgA and 23.3–60% to IgG. Finally, we detected the presence of the subclasses IgG1, IgG2, and IgG4 against all the structural proteins of SARS-CoV-2. Conclusions: This work provides evidence of the presence of IgA and IgG antibodies against the four structural proteins of SARS-CoV-2 in breast milk and serum samples derived from breastfeeding women, which can confer immunity to the newborn. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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8 pages, 5045 KiB

Open AccessCommunication

Seroprevalence of IgG and Subclasses against the Nucleocapsid of SARS-CoV-2 in Health Workers

by Karen Cortés-Sarabia, Kenet Hisraim Palomares-Monterrubio, Jesús Omar Velázquez-Moreno, Víctor Manuel Luna-Pineda, Marco Antonio Leyva-Vázquez, Amalia Vences-Velázquez, Roberto Dircio-Maldonado, Oscar Del Moral-Hernández and Berenice Illades-Aguiar

Viruses 2023, 15(4), 955; https://0-doi-org.brum.beds.ac.uk/10.3390/v15040955 - 13 Apr 2023

Cited by 2 | Viewed by 1426

Abstract

Background: The nucleocapsid protein of SARS-CoV-2 participates in viral replication, transcription, and assembly. Antibodies against this protein have been proposed for the epidemiological analysis of the seroprevalence of COVID-19 associated with natural infection by SARS-CoV-2. Health workers were one of the most exposed populations, and some had an asymptomatic form of the disease, so detecting IgG antibodies and subclasses against the N protein can help to reclassify their epidemiological status and obtain information about the effector mechanisms associated with viral elimination. Methods: In this study, we analyzed 253 serum samples collected in 2021 and derived from health workers, and evaluated the presence of total IgG and subclasses against the N protein of SARS-CoV-2 by indirect ELISA. Results: From the analyzed samples, 42.69% were positive to anti-N IgG antibodies. A correlation between COVID-19 asymptomatic infection and IgG antibodies was observed (p = 0.006). The detected subclasses were: IgG1 (82.4%), IgG2 (75.9%), IgG3 (42.6%), and IgG4 (72.6%). Conclusions: This work provides evidence about the high seroprevalence of total IgG and subclasses of anti-N and their relations with the asymptomatic infection of SARS-CoV-2 and related symptoms. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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8 pages, 2600 KiB

Open AccessCommunication

Importance of Cellular Immunity and IFN-γ Concentration in Preventing SARS-CoV-2 Infection and Reinfection: A Cohort Study

by Dragan Primorac, Petar Brlek, Eduard Stjepan Pavelić, Jana Mešić, David Glavaš Weinberger, Vid Matišić, Vilim Molnar, Saša Srića and Renata Zadro

Viruses 2023, 15(3), 792; https://0-doi-org.brum.beds.ac.uk/10.3390/v15030792 - 20 Mar 2023

Cited by 4 | Viewed by 1835

Abstract

Recent studies have highlighted the underestimated importance of the cellular immune response after the emergence of variants of concern (VOCs) of SARS-CoV-2, and the significantly reduced neutralizing power of antibody titers in individuals with previous SARS-CoV-2 infection or vaccination. Our study included 303 participants who were tested at St. Catherine Specialty Hospital using the Quan-T-Cell SARS-CoV-2 in combination with the Quan-T-Cell ELISA (Euroimmun Medizinische Labordiagnostika, Lübeck, Germany) for the analysis of IFN-γ concentration, and with Anti-SARS-CoV-2 QuantiVac ELISA IgG (Euroimmun Medizinische Labordiagnostika, Lübeck, Germany) for the detection of human antibodies of the immunoglobulin class IgG against the S1 domain of the SARS-CoV-2 spike protein. The statistical analysis showed a significant difference in the concentration of IFN-γ between reinfected participants and those without infection (p = 0.012). Participants who were not infected or reinfected with SARS-CoV-2 after vaccination and/or previous SARS-CoV-2 infection had a significantly higher level of cellular immunity. Furthermore, in individuals without additional vaccination, those who experienced infection/reinfection had significantly lower levels of IFN-γ compared to uninfected participants (p = 0.016). Our findings suggest a long-lasting effect of cellular immunity, measured by IFN-γ concentrations, which plays a key role in preventing infections and reinfections after the emergence of SARS-CoV-2 variants of concern. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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18 pages, 1545 KiB

Open AccessArticle

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study)

by Yulia Alexandrova, Alexis Yero, Ralph-Sydney Mboumba Bouassa, Eve Comeau, Suzanne Samarani, Zabrina L. Brumme, Mark Hull, Angela M. Crawley, Marc-André Langlois, Jonathan B. Angel, Curtis L. Cooper, Judy Needham, Terry Lee, Joel Singer, Aslam H. Anis, Cecilia T. Costiniuk and Mohammad-Ali Jenabian

Viruses 2023, 15(2), 575; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020575 - 19 Feb 2023

Cited by 5 | Viewed by 2609

Abstract

People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection. Flow cytometry was used to assess ex vivo T-cell immunophenotypes and intracellular Tumor necrosis factor (TNF)-α/interferon(IFN)-γ/interleukin(IL)-2 following SARS-CoV-2-Spike-peptide stimulation. Comparisons were made using Wilcoxon signed-rank test for paired variables and Mann–Whitney for unpaired. In PLWH, Spike-specific CD4 T-cell frequencies plateaued post-2nd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. PLWH had higher frequencies of TNFα+CD4 T-cells and lower frequencies of IFNγ+CD8 T-cells than seronegative participants post-3rd dose. Regardless of HIV status, an increase in naive, regulatory, and PD1+ T-cell frequencies was observed post-3rd dose. In summary, two doses of SARS-CoV-2 vaccine induced a robust T-cell immune response in PLWH, which was maintained after the 3rd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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10 pages, 927 KiB

Open AccessCommunication

Early Treatment with Monoclonal Antibodies or Convalescent Plasma Reduces Mortality in Non-Vaccinated COVID-19 High-Risk Patients

by Laura Thümmler, Monika Lindemann, Peter A. Horn, Veronika Lenz, Margarethe Konik, Anja Gäckler, Kristina Boss, Fotis Theodoropoulos, Vasiliki Besa, Christian Taube, Thorsten Brenner, Oliver Witzke, Adalbert Krawczyk and Hana Rohn

Viruses 2023, 15(1), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/v15010119 - 30 Dec 2022

Cited by 6 | Viewed by 1846

Abstract

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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10 pages, 970 KiB

Open AccessArticle

Immune Response after the Fourth Dose of SARS-CoV-2 mRNA Vaccine Compared to Natural Infection in Three Doses’ Vaccinated Solid Organ Transplant Recipients

by Rosalia Busà, Giovanna Russelli, Monica Miele, Maria Concetta Sorrentino, Mariangela Di Bella, Francesca Timoneri, Giuseppina Di Mento, Alessandra Mularoni, Patrizio Vitulo, Pier Giulio Conaldi and Matteo Bulati

Viruses 2022, 14(10), 2299; https://0-doi-org.brum.beds.ac.uk/10.3390/v14102299 - 19 Oct 2022

Cited by 8 | Viewed by 1943

Abstract

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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10 pages, 959 KiB

Open AccessBrief Report

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients

by Jakub Wroński, Bożena Jaszczyk, Leszek Roszkowski, Anna Felis-Giemza, Krzysztof Bonek, Anna Kornatka, Magdalena Plebańczyk, Tomasz Burakowski, Barbara Lisowska, Brygida Kwiatkowska, Włodzimierz Maśliński, Małgorzata Wisłowska, Magdalena Massalska, Ewa Kuca-Warnawin and Marzena Ciechomska

Viruses 2023, 15(3), 620; https://0-doi-org.brum.beds.ac.uk/10.3390/v15030620 - 24 Feb 2023

Cited by 2 | Viewed by 1195

Abstract

Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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11 pages, 296 KiB

Open AccessOpinion

Do We Really Need Omicron Spike-Based Updated COVID-19 Vaccines? Evidence and Pipeline

by Daniele Focosi and Fabrizio Maggi

Viruses 2022, 14(11), 2488; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112488 - 10 Nov 2022

Cited by 5 | Viewed by 2684

Abstract

The wild-type SARS-CoV-2 Spike-based vaccines authorized so far have reduced COVID-19 severity, but periodic boosts are required to counteract the decline in immunity. An accelerated rate of immune escape to vaccine-elicited immunity has been associated with Spike protein antigenic shifts, as seen in the Omicron variant of concern and its sublineages, demanding the development of Omicron Spike-based vaccines. Herein, we review the evidence in animal models and topline results from ongoing clinical trials with such updated vaccines, discussing the pros and cons for their deployment. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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