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Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Coronaviruses".

Deadline for manuscript submissions: closed (5 April 2024) | Viewed by 7222

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Special Issue Editor

Dr. Pablo Barreiro

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Guest Editor

Regional Laboratory of Public Health, “La Paz” University Hospital, Rey Juan Carlos University, Madrid, Spain
Interests: infectious diseases; viruses; tropical medicine; artificial inteligence; bioethics

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has posed an unprecedented global health crisis, demanding swift and effective measures to combat its devastating impact. Vaccination has emerged as a vital tool in the fight against the virus, providing hope for a return to normalcy. Multiple vaccine platforms have demonstrated impressive immunogenicity profiles, successfully eliciting neutralizing antibodies, T-cell responses, and memory immune cells. Real-world studies have proven the effectiveness of these vaccines in reducing symptomatic infections, severe disease, hospitalizations, and deaths. The immunogenicity of COVID-19 vaccines has not only provided protection at the individual level but also contributed to the larger goal of achieving population-wide immunity and curtailing the spread of the virus. Once the WHO is no longer considering the SARS-CoV pandemic a global health threat, there are still unanswered questions that deserve further investigations. How durable may be the protective effect of these vaccines? What is the recommended vaccination schedule? Are there differences in these schedules by risk groups or among different compounds? Do we need to consider in the future global vaccination or just for selected groups? What is the long-term safety of these vaccines? Are there specific concerns affecting certain platforms? What do we know about the efficacy and safety of vaccines that have not been subject to surveillance by EU or US agencies? The special issue entitled “Immunogenicity and Safety of COVID-19 Vaccines” of the journal Viruses scheduled for publication along the first months of 2024 will address these and other burning issues related with SARS-CoV-2 vaccines.

Dr. Pablo Barreiro
Guest Editor

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Keywords

SARS-CoV-2
COVID-19
vaccines
immunogenicity
safety
RNA-vaccines
prevention

Published Papers (8 papers)

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16 pages, 2050 KiB

Open AccessArticle

T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy

by Sneha Datwani, Rebecca Kalikawe, Rachel Waterworth, Francis M. Mwimanzi, Richard Liang, Yurou Sang, Hope R. Lapointe, Peter K. Cheung, Fredrick Harrison Omondi, Maggie C. Duncan, Evan Barad, Sarah Speckmaier, Nadia Moran-Garcia, Mari L. DeMarco, Malcolm Hedgcock, Cecilia T. Costiniuk, Mark Hull, Marianne Harris, Marc G. Romney, Julio S. G. Montaner, Zabrina L. Brumme and Mark A. Brockman Show full author list Hide full author list

Viruses 2024, 16(5), 661; https://doi.org/10.3390/v16050661 - 24 Apr 2024

Viewed by 260

Abstract

People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all p < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose (p > 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose (p = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables (p = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses (p < 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose (p = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

19 pages, 7301 KiB

Open AccessArticle

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters

by Zhi-Hui Yang, Yan-Li Song, Jie Pei, Song-Zhuang Li, Rui-Lun Liu, Yu Xiong, Jie Wu, Yuan-Lang Liu, Hui-Fen Fan, Jia-Hui Wu, Ze-Jun Wang, Jing Guo, Sheng-Li Meng, Xiao-Qi Chen, Jia Lu and Shuo Shen

Viruses 2024, 16(4), 559; https://doi.org/10.3390/v16040559 - 03 Apr 2024

Viewed by 671

Abstract

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2). Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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29 pages, 3257 KiB

Open AccessArticle

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

by Sabrina Clever, Leonard Limpinsel, Christian Meyer zu Natrup, Lisa-Marie Schünemann, Georg Beythien, Malgorzata Rosiak, Kirsten Hülskötter, Katharina Manuela Gregor, Tamara Tuchel, Georgia Kalodimou, Astrid Freudenstein, Satendra Kumar, Wolfgang Baumgärtner, Gerd Sutter, Alina Tscherne and Asisa Volz

Viruses 2024, 16(3), 417; https://doi.org/10.3390/v16030417 - 08 Mar 2024

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Abstract

The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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12 pages, 1207 KiB

Open AccessArticle

Factors Associated with SARS-CoV-2 Infection in Fully Vaccinated Nursing Home Residents and Workers

by Jesús Mateos-Nozal, Mario Rodríguez-Domínguez, Jesús San Román, Francisco Javier Candel, Noelia Villarrubia, Nuria Pérez-Panizo, Esther Segura, Juan Manuel Cuñarro, Manuel V. Mejía Ramírez-Arellano, Rafael Rodríguez-Ramos, Roberto Pariente-Rodríguez, Luisa M. Villar, Primitivo Ramos, Rafael Cantón, Alfonso J. Cruz-Jentoft and Juan Carlos Galán

Viruses 2024, 16(2), 186; https://doi.org/10.3390/v16020186 - 25 Jan 2024

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Abstract

Persons living or working in nursing homes faced a higher risk of SARS-CoV-2 infections during the pandemic, resulting in heightened morbidity and mortality among older adults despite robust vaccination efforts. This prospective study evaluated the humoral and cellular immunity in fully vaccinated residents and workers from two nursing homes in Madrid, Spain, from 2020 to 2021. Measurements of IgG levels were conducted in August 2020 (pre-vaccination) and June and September 2021 (post-vaccination), alongside assessments of neutralizing antibodies and cellular responses in September 2021 among the most vulnerable individuals. Follow-up extended until February 2022 to identify risk factors for SARS-CoV-2 infection or mortality, involving 267 residents (mean age 87.6 years, 81.3% women) and 302 workers (mean age 50.7 years, 82.1% women). Residents exhibited a significantly higher likelihood of experiencing COVID-19 before June 2021 compared with nursing staff (OR [95% CI], 7.2 [3.0 to 17.2], p < 0.01). Participants with a history of previous COVID-19 infection showed more significant increases in IgG levels in August 2020, June 2021 and September 2021, alongside an increased proportion of neutralizing antibodies in the most vulnerable individuals. However, IgG decay remained the same between June and September 2021 based on the previous COVID-19 status. During the Omicron variant wave, residents and staff showed a similar rate of SARS-CoV-2 infection. Notably, preceding clinical or immunological factors before receiving three vaccination doses did not demonstrate associations with COVID-19 infection or overall mortality in our participant cohort. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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13 pages, 1999 KiB

Open AccessArticle

Seven Epidemic Waves of COVID-19 in a Hospital in Madrid: Analysis of Severity and Associated Factors

by Juan Víctor San Martín-López, Nieves Mesa, David Bernal-Bello, Alejandro Morales-Ortega, Marta Rivilla, Marta Guerrero, Ruth Calderón, Ana I. Farfán, Luis Rivas, Guillermo Soria, Aída Izquierdo, Elena Madroñal, Miguel Duarte, Sara Piedrabuena, María Toledano-Macías, Jorge Marrero, Cristina de Ancos, Begoña Frutos, Rafael Cristóbal, Laura Velázquez, Belén Mora, Paula Cuenca, José Á. Satué, Ibone Ayala-Larrañaga, Lorena Carpintero, Celia Lara, Álvaro R. Llerena, Virginia García, Vanessa García de Viedma, Santiago Prieto, Natalia González-Pereira, Cristina Bravo, Carolina Mariño, Luis Antonio Lechuga, Jorge Tarancón, Sonia Gonzalo, Santiago Moreno and José M. Ruiz-Giardin Show full author list Hide full author list

Viruses 2023, 15(9), 1839; https://doi.org/10.3390/v15091839 - 30 Aug 2023

Cited by 1 | Viewed by 1069

Abstract

(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07–1.09), cancer (OR: 1.99, 1.53–2.60), dementia (OR: 1.82, 1.20–2.75), the Charlson index (1.38, 1.31–1.47), the need for high-flow oxygen (OR: 6.10, 4.94–7.52), mechanical ventilation (OR: 11.554, 6.996–19.080), and CRP (OR: 1.04, 1.03–1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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13 pages, 488 KiB

Open AccessArticle

Predictors of SARS-CoV-2 Infection and Severe and Lethal COVID-19 after Three Years of Follow-Up: A Population-Wide Study

by Maria Elena Flacco, Cecilia Acuti Martellucci, Graziella Soldato, Giuseppe Di Martino, Annalisa Rosso, Roberto Carota, Marco De Benedictis, Graziano Di Marco, Rossano Di Luzio, Matteo Ricci, Antonio Caponetti, Davide Gori and Lamberto Manzoli

Viruses 2023, 15(9), 1794; https://doi.org/10.3390/v15091794 - 24 Aug 2023

Viewed by 1082

Abstract

In this cohort study, the general population of an Italian Province was followed for three years after the start of the pandemic, in order to identify the predictors of SARS-CoV-2 infection and severe or lethal COVID-19. All the National Healthcare System information on biographical records, vaccinations, SARS-CoV-2 swabs, COVID-19 cases, hospitalizations and co-pay exemptions were extracted from 25 February 2020 to 15 February 2023. Cox proportional hazard analysis was used to compute the relative hazards of infection and severe or lethal COVID-19, adjusting for age, gender, vaccine status, hypertension, diabetes, major cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), kidney disease or cancer. Among the 300,079 residents or domiciled citizens, 41.5% had ≥1 positive swabs during the follow-up (which lasted a mean of 932 days). A total of 3.67% of the infected individuals experienced severe COVID-19 (n = 4574) and 1.76% died (n = 2190). Females, the elderly and subjects with diabetes, CVD, COPD, kidney disease and cancer showed a significantly higher risk of SARS-CoV-2 infection. The likelihood of severe or lethal COVID-19 was >90% lower among the youngest, and all comorbidities were independently associated with a higher risk (ranging from +28% to +214%) of both outcomes. Two years after the start of the immunization campaign, the individuals who received ≥2 doses of COVID-19 vaccines still showed a significantly lower likelihood of severe or lethal disease, with the lowest risk observed among subjects who received at least one booster dose. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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21 pages, 962 KiB

Open AccessArticle

Differences in Trends in Admissions and Outcomes among Patients from a Secondary Hospital in Madrid during the COVID-19 Pandemic: A Hospital-Based Epidemiological Analysis (2020–2022)

by Rafael Garcia-Carretero, Oscar Vazquez-Gomez, María Ordoñez-Garcia, Noelia Garrido-Peño, Ruth Gil-Prieto and Angel Gil-de-Miguel

Viruses 2023, 15(7), 1616; https://doi.org/10.3390/v15071616 - 24 Jul 2023

Cited by 2 | Viewed by 1001

Abstract

Spain had some of Europe’s highest incidence and mortality rates for coronavirus disease 2019 (COVID-19). This study highlights the impact of the COVID-19 pandemic on daily health care in terms of incidence, critical patients, and mortality. We describe the characteristics and clinical outcomes of patients, comparing variables over the different waves. We performed a descriptive, retrospective study using the historical records of patients hospitalized with COVID-19. We describe demographic characteristics, admissions, and occupancy. Time series allowed us to visualize and analyze trends and patterns, and identify several waves during the 27-month period. A total of 3315 patients had been hospitalized with confirmed COVID-19. One-third of these patients were hospitalized during the first weeks of the pandemic. We observed that 4.6% of all hospitalizations had been admitted to the intensive care unit, and we identified a mortality rate of 9.4% among hospitalized patients. Arithmetic- and semi-logarithmic-scale charts showed how admissions and deaths rose sharply during the first weeks, increasing by 10 every few days. We described a single hospital’s response and experiences during the pandemic. This research highlights certain demographic profiles in a population and emphasizes the importance of identifying waves when performing research on COVID-19. Our results can extend the analysis of the impact of COVID-19 and can be applied in other contexts, and can be considered when further analyzing the clinical, epidemiological, or demographic characteristics of populations with COVID-19. Our findings suggest that the pandemic should be analyzed not as a whole but rather in different waves. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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15 pages, 865 KiB

Open AccessBrief Report

Humoral Immune Responses after an Omicron-Adapted Booster BNT162b2 Vaccination in Patients with Lymphoid Malignancies

by Line Dam Heftdal, Cecilie Bo Hansen, Sebastian Rask Hamm, Laura Pérez-Alós, Kamille Fogh, Mia Pries-Heje, Rasmus Bo Hasselbalch, Dina Leth Møller, Anne Ortved Gang, Sisse Rye Ostrowski, Ruth Frikke-Schmidt, Erik Sørensen, Linda Hilsted, Henning Bundgaard, Peter Garred, Kasper Iversen, Caroline Sabin, Susanne Dam Nielsen and Kirsten Grønbæk

Viruses 2024, 16(1), 11; https://doi.org/10.3390/v16010011 (registering DOI) - 20 Dec 2023

Viewed by 889

Abstract

To accommodate waning COVID-19 vaccine immunity to emerging SARS-CoV-2 variants, variant-adapted mRNA vaccines have been introduced. Here, we examine serological responses to the BA.1 and BA.4-5 Omicron variant-adapted BNT162b2 COVID-19 vaccines in people with lymphoid malignancies. We included 233 patients with lymphoid malignancies (chronic lymphocytic B-cell leukemia: 73 (31.3%), lymphoma: 89 (38.2%), multiple myeloma/amyloidosis: 71 (30.5%)), who received an Omicron-adapted mRNA-based COVID-19 vaccine. IgG and neutralizing antibodies specific for the receptor-binding domain (RBD) of SARS-CoV-2 were measured using ELISA-based methods. Differences in antibody concentrations and neutralizing capacity and associations with risk factors were assessed using mixed-effects models. Over the period of vaccination with an Omicron-adapted COVID-19 vaccine, the predicted mean concentration of anti-RBD IgG increased by 0.09 log10 AU/mL/month (95% CI: 0.07; 0.11) in patients with lymphoid malignancies across diagnoses. The predicted mean neutralizing capacity increased by 0.9 percent points/month (95% CI: 0.2; 1.6). We found no associations between the increase in antibody concentration or neutralizing capacity and the variant included in the adapted vaccine. In conclusion, a discrete increase in antibody concentrations and neutralizing capacity was found over the course of Omicron-adapted vaccination in patients with lymphoid malignancies regardless of the adapted vaccine variant, indicating a beneficial effect of Omicron-adapted booster vaccination in this population. Full article

(This article belongs to the Special Issue Immunogenicity and Safety of COVID-19 Vaccine: A Milestone Achieved in the Battle against the Pandemic)

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