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19 pages, 2249 KiB

Open AccessArticle

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

by Yoshihiro Watanabe, Natsuko Hosokawa, Misaki Yoshida, Tomoyuki Miura and Mitsuhiro Kawano

Vaccines 2023, 11(2), 287; https://doi.org/10.3390/vaccines11020287 - 28 Jan 2023

Cited by 1 | Viewed by 1660

Abstract

SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response to Spike antigens is effective, but similar vaccines could not enhance Ab efficacy enough. Effective Ab responses against the human ACE2 (hACE2)-mediated infection of the emerging SARS-CoV-2 variants are needed. We [...] Read more.

SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response to Spike antigens is effective, but similar vaccines could not enhance Ab efficacy enough. Effective Ab responses against the human ACE2 (hACE2)-mediated infection of the emerging SARS-CoV-2 variants are needed. We identified closed linear epitopes of the SARS-CoV-2 Spike molecule that induced neutralizing Abs (nAbs) against both S1-RBD, responsible for attachment to hACE2, and S2-HR1/2, in convalescents and vaccine recipients. They inhibited a pseudo-virus infection mediated by the hACE2 pathway. The epitope sequences included epitopes #7 (aa411-432), #11 (aa459-480) and #111 (aa1144-1161), in S1-RBD and S2-HR2. Epitope #111 was conserved in Wuhan and variant strains, whereas #7 and #11 were conserved in Wuhan carried mutations K417N and S477N/T478K in Omicron BA.4/5. These mutations were recognized by the original epitope-specific Abs. These epitopes in RBD and HR2 neither contained, nor overlapped with, those responsible for the antibody-dependent enhancement of the SARS-CoV-2 infection. The sublingual administration of multiple epitope-conjugated antigens increased the IgG and IgA Abs specific to the neutralizing epitopes in mice pre-immunized subcutaneously. The findings indicated that S1-RBD and S2-HR2 epitopes were responsible for pseudo-virus SARS-CoV-2 infections and that sublingual boosts with multiple epitope-conjugated antigens could enhance the protection by nAbs of IgG and IgA against infection by a wide range of variants. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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13 pages, 1911 KiB

Open AccessArticle

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma

by Luigino Calzetta, Alfredo Chetta, Marina Aiello, Annalisa Frizzelli, Josuel Ora, Enrico Melis, Francesco Facciolo, Lorenzo Ippoliti, Andrea Magrini and Paola Rogliani

Vaccines 2023, 11(2), 282; https://doi.org/10.3390/vaccines11020282 - 28 Jan 2023

Cited by 2 | Viewed by 2793

Abstract

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute [...] Read more.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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10 pages, 650 KiB

Open AccessArticle

Ageing Curtails the Diversity and Functionality of Nascent CD8⁺ T Cell Responses against SARS-CoV-2

by Davide Proietto, Beatrice Dallan, Eleonora Gallerani, Valentina Albanese, Sian Llewellyn-Lacey, David A. Price, Victor Appay, Salvatore Pacifico, Antonella Caputo, Francesco Nicoli and Riccardo Gavioli

Vaccines 2023, 11(1), 154; https://doi.org/10.3390/vaccines11010154 - 11 Jan 2023

Cited by 1 | Viewed by 1550

Abstract

Age-related changes in the immune system are thought to underlie the vulnerability of elderly individuals to emerging viral diseases, such as coronavirus disease 2019 (COVID-19). In this study, we used a fully validated in vitro approach to determine how age impacts the generation [...] Read more.

Age-related changes in the immune system are thought to underlie the vulnerability of elderly individuals to emerging viral diseases, such as coronavirus disease 2019 (COVID-19). In this study, we used a fully validated in vitro approach to determine how age impacts the generation of de novo CD8⁺ T cell responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. Our data revealed a generalized deficit in the ability of elderly individuals to prime the differentiation of naïve precursors into effector CD8⁺ T cells defined by the expression of interferon (IFN)-γ and the transcription factor T-bet. As a consequence, there was an age-related decline in the diversity of newly generated CD8⁺ T cell responses targeting a range of typically immunodominant epitopes derived from SARS-CoV-2, accompanied by an overall reduction in the expression frequency of IFN-γ. These findings have potential implications for the development of new strategies to protect the elderly against COVID-19. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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14 pages, 1413 KiB

Open AccessArticle

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients

by Monica Basso, Nicole Pirola, Susanna Pascoli, Beatrice Bragato, Antonio Vinci, Marco Iannetta, Francesco Colombo, Nicholas Geremia, Luca Martignago, Maria Cristina Rossi, Ludovica Cipriani, Mario Giobbia, Pier Giorgio Scotton and Saverio Giuseppe Parisi

Vaccines 2023, 11(1), 82; https://doi.org/10.3390/vaccines11010082 - 30 Dec 2022

Cited by 5 | Viewed by 1496

Abstract

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of [...] Read more.

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm³ and the median nadir value was 258 cells/mm³. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th–25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm³ had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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27 pages, 3034 KiB

Open AccessArticle

Thermophilic Filamentous Fungus C1-Cell-Cloned SARS-CoV-2-Spike-RBD-Subunit-Vaccine Adjuvanted with Aldydrogel^®85 Protects K18-hACE2 Mice against Lethal Virus Challenge

by Ram Nechooshtan, Sharon Ehrlich, Marika Vitikainen, Arik Makovitzki, Eyal Dor, Hadar Marcus, Idan Hefetz, Shani Pitel, Marilyn Wiebe, Anne Huuskonen, Lilach Cherry, Edith Lupu, Yehuda Sapir, Tzvi Holtzman, Moshe Aftalion, David Gur, Hadas Tamir, Yfat Yahalom-Ronen, Yuval Ramot, Noam Kronfeld, David Zarling, Anne Vallerga, Ronen Tchelet, Abraham Nyska, Markku Saloheimo, Mark Emalfarb and Yakir Ophir Show full author list Hide full author list

Vaccines 2022, 10(12), 2119; https://doi.org/10.3390/vaccines10122119 - 11 Dec 2022

Cited by 4 | Viewed by 2337

Abstract

SARS-CoV-2 is evolving with increased transmission, host range, pathogenicity, and virulence. The original and mutant viruses escape host innate (Interferon) immunity and adaptive (Antibody) immunity, emphasizing unmet needs for high-yield, commercial-scale manufacturing to produce inexpensive vaccines/boosters for global/equitable distribution. We developed DYAI-100A85, a [...] Read more.

SARS-CoV-2 is evolving with increased transmission, host range, pathogenicity, and virulence. The original and mutant viruses escape host innate (Interferon) immunity and adaptive (Antibody) immunity, emphasizing unmet needs for high-yield, commercial-scale manufacturing to produce inexpensive vaccines/boosters for global/equitable distribution. We developed DYAI-100A85, a SARS-CoV-2 spike receptor binding domain (RBD) subunit antigen vaccine expressed in genetically modified thermophilic filamentous fungus, Thermothelomyces heterothallica C1, and secreted at high levels into fermentation medium. The RBD-C-tag antigen strongly binds ACE2 receptors in vitro. Alhydrogel^®‘85’-adjuvanted RDB-C-tag-based vaccine candidate (DYAI-100A85) demonstrates strong immunogenicity, and antiviral efficacy, including in vivo protection against lethal intranasal SARS-CoV-2 (D614G) challenge in human ACE2-transgenic mice. No loss of body weight or adverse events occurred. DYAI-100A85 also demonstrates excellent safety profile in repeat-dose GLP toxicity study. In summary, subcutaneous prime/boost DYAI-100A85 inoculation induces high titers of RBD-specific neutralizing antibodies and protection of hACE2-transgenic mice against lethal challenge with SARS-CoV-2. Given its demonstrated safety, efficacy, and low production cost, vaccine candidate DYAI-100 received regulatory approval to initiate a Phase 1 clinical trial to demonstrate its safety and efficacy in humans. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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17 pages, 1888 KiB

Open AccessArticle

Understanding Influenza and SARS-CoV-2 Vaccine Hesitancy in Racial and Ethnic Minority Caregivers

by Shannon H. Baumer-Mouradian, Rebecca J. Hart, Alexis Visotcky, Raphael Fraser, Swathi Prasad, Michael Levas, Mark Nimmer and David C. Brousseau

Vaccines 2022, 10(11), 1968; https://doi.org/10.3390/vaccines10111968 - 20 Nov 2022

Cited by 6 | Viewed by 1584

Abstract

(1) Background: We compared influenza and SARS-CoV-2 vaccine hesitancy levels in Black, Hispanic, and White parents/caregivers and identified barriers and facilitators to vaccine acceptance. (2) Methods: This was a mixed methods study. A cross-sectional survey of ED caregivers presenting with children 6mo–18yo compared [...] Read more.

(1) Background: We compared influenza and SARS-CoV-2 vaccine hesitancy levels in Black, Hispanic, and White parents/caregivers and identified barriers and facilitators to vaccine acceptance. (2) Methods: This was a mixed methods study. A cross-sectional survey of ED caregivers presenting with children 6mo–18yo compared vaccine hesitancy levels among diverse caregivers. Six focus groups of survey participants, stratified by caregiver race/ethnicity and caregiver intent to receive SARS-CoV-2 vaccine, assessed facilitators and barriers of vaccination, with thematic coding using the Consolidated Framework for Implementation Research (CFIR). (3) Results: Surveys (n = 589) revealed Black caregivers had significantly higher vaccine hesitancy rates than White caregivers for pediatric influenza (42% versus 21%) and SARS-CoV-2 (63% versus 36%; both p < 0.05). Hispanic caregivers were more hesitant than White caregivers (37% flu and 58% SARS-CoV-2), but this was not significant. Qualitative analysis (n = 23 caregivers) identified barriers including vaccine side effects, lack of necessity, inadequate data/science, and distrust. Facilitators included vaccine convenience, fear of illness, and desire to protect others. (4) Conclusions: Minority caregivers reported higher levels of vaccine hesitancy for influenza and SARS-CoV-2. We identified vaccine facilitators and barriers inclusive of Black and Hispanic caregivers, which may guide interventions designed to equitably improve acceptance of pediatric vaccines. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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10 pages, 422 KiB

Open AccessArticle

A Framework for Inspiring COVID-19 Vaccine Confidence in African American and Latino Communities

by Zanthia Wiley, Lana Khalil, Kennedy Lewis, Matthew Lee, Maranda Leary, Valeria D. Cantos, Ighovwerha Ofotokun, Nadine Rouphael and Paulina A. Rebolledo

Vaccines 2022, 10(8), 1319; https://doi.org/10.3390/vaccines10081319 - 15 Aug 2022

Cited by 10 | Viewed by 2216

Abstract

The COVID-19 pandemic has disproportionately impacted racial and ethnic minority communities, particularly African American and Latino communities. The impacts of social determinants of health, structural racism, misinformation, and mistrust have contributed to a decreased COVID-19 vaccine uptake. Effective methods of addressing and combatting [...] Read more.

The COVID-19 pandemic has disproportionately impacted racial and ethnic minority communities, particularly African American and Latino communities. The impacts of social determinants of health, structural racism, misinformation, and mistrust have contributed to a decreased COVID-19 vaccine uptake. Effective methods of addressing and combatting these barriers are essential. Accurate and targeted messaging delivered by trusted voices from community-based organizations, government health systems and organizations, and healthcare and academic systems is imperative. Outreach and communication should be culturally sensitive, provided in the preferred language of the community, flexible, and tailored for in-person and virtual outlets. This communication must also increase trust, combat misinformation, and inspire COVID-19 vaccine confidence. In this manuscript, we outline a framework for inspiring COVID-19 vaccine confidence in African American and Latino communities. These methods of targeted outreach should be considered and implemented for urgent and nonurgent community public health efforts beyond the COVID-19 pandemic (e.g., monkeypox) and as a framework to inspire vaccine confidence in those living in racial and ethnic minority communities globally. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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13 pages, 1832 KiB

Open AccessArticle

Effectiveness of Booster Dose of Anti SARS-CoV-2 BNT162b2 in Cirrhosis: Longitudinal Evaluation of Humoral and Cellular Response

by Vincenzo Giambra, Annarita Valeria Piazzolla, Giovanna Cocomazzi, Maria Maddalena Squillante, Elisabetta De Santis, Beatrice Totti, Chiara Cavorsi, Francesco Giuliani, Nicola Serra and Alessandra Mangia

Vaccines 2022, 10(8), 1281; https://doi.org/10.3390/vaccines10081281 - 08 Aug 2022

Cited by 12 | Viewed by 1522

Abstract

Background: LC has been associated with hyporesponsiveness to several vaccines. Nonetheless, no data on complete serological and B- and T-cell immune response are currently available. Aims: To assess, in comparison with healthy controls of the same age and gender, both humoral and cellular [...] Read more.

Background: LC has been associated with hyporesponsiveness to several vaccines. Nonetheless, no data on complete serological and B- and T-cell immune response are currently available. Aims: To assess, in comparison with healthy controls of the same age and gender, both humoral and cellular immunoresponses of patients with LC after two or three doses of the mRNA Pfizer-BioNTech vaccine against SARS-CoV-2 and to investigate clinical features associated with non-response. Material and methods: 179 patients with LC of CTP class A in 93.3% and viral etiology in 70.1% of cases were longitudinally evaluated starting from the day before the first dose to 4 weeks after the booster dose. Their antibody responses were compared to those of healthcare workers without co-morbidities. In a subgroup of 40 patients, B- and T-cell responses were also compared to controls. Results: At d31, d90 and d180 after BNT162b2 vaccine, no detectable SARS-CoV-2 IgG response was observed in 5.9%, 3.9% and 7.2% of LC patients as compared to 0 controls (p < 0.03). A delay in B-cell and lack of prompt T-cell response compared to healthcare workers was also registered. A significant correlation between antibody titers and cellular response was observed. A MELD score > 8 was the only independent predictor of poor d31 response (p = 0.028). Conclusions: Our results suggest that cirrhotic patients have a slower and in <10% suboptimal immune response to SARS-CoV-2 vaccination. Rates of breakthrough infections were comparable between cirrhotics and controls. The booster dose was critical in inducing both humoral and cellular responses comparable to controls. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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9 pages, 1080 KiB

Open AccessArticle

Long-Term Longitudinal Analysis of Neutralizing Antibody Response to Three Vaccine Doses in a Real-Life Setting of Previously SARS-CoV-2 Infected Healthcare Workers: A Model for Predicting Response to Further Vaccine Doses

by Saverio Giuseppe Parisi, Carlo Mengoli, Monica Basso, Ilaria Vicenti, Francesca Gatti, Renzo Scaggiante, Lia Fiaschi, Federica Giammarino, Marco Iannetta, Vincenzo Malagnino, Daniela Zago, Filippo Dragoni and Maurizio Zazzi

Vaccines 2022, 10(8), 1237; https://doi.org/10.3390/vaccines10081237 - 02 Aug 2022

Cited by 1 | Viewed by 1426

Abstract

We report the time course of neutralizing antibody (NtAb) response, as measured by authentic virus neutralization, in healthcare workers (HCWs) with a mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection diagnosed at the onset of the pandemic, with no reinfection [...] Read more.

We report the time course of neutralizing antibody (NtAb) response, as measured by authentic virus neutralization, in healthcare workers (HCWs) with a mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection diagnosed at the onset of the pandemic, with no reinfection throughout and after a three-dose schedule of the BNT162b2 mRNA vaccine with an overall follow-up of almost two years since infection. Forty-eight HCWs (median age 47 years, all immunocompetent) were evaluated: 29 (60.4%) were asymptomatic. NtAb serum was titrated at eight subsequent time points: T1 and T2 were after natural infection, T3 on the day of the first vaccine dose, T4 on the day of the second dose, T5, T6, and T7 were between the second and third dose, and T8 followed the third dose by a median of 34 days. NtAb titers at all postvaccination time points (T4 to T8) were significantly higher than all those at prevaccination time points (T1 to T3). The highest NtAb increase was following the first vaccine dose while subsequent doses did not further boost NtAb titers. However, the third vaccine dose appeared to revive waning immunity. NtAb levels were positively correlated at most time points suggesting an important role for immunogenetics. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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14 pages, 2608 KiB

Open AccessArticle

Activation of Anti-SARS-CoV-2 Human CTLs by Extracellular Vesicles Engineered with the N Viral Protein

by Francesco Manfredi, Chiara Chiozzini, Flavia Ferrantelli, Patrizia Leone, Andrea Giovannelli, Massimo Sanchez and Maurizio Federico

Vaccines 2022, 10(7), 1060; https://doi.org/10.3390/vaccines10071060 - 30 Jun 2022

Cited by 3 | Viewed by 1558

Abstract

We propose an innovative anti-SARS-CoV-2 immune strategy based on extracellular vesicles (EVs) inducing an anti-SARS-CoV-2 N CD8⁺ T cytotoxic lymphocyte (CTL) immune response. We previously reported that the SARS-CoV-2 N protein can be uploaded at high levels in EVs upon fusion with [...] Read more.

We propose an innovative anti-SARS-CoV-2 immune strategy based on extracellular vesicles (EVs) inducing an anti-SARS-CoV-2 N CD8⁺ T cytotoxic lymphocyte (CTL) immune response. We previously reported that the SARS-CoV-2 N protein can be uploaded at high levels in EVs upon fusion with Nef^mut, i.e., a biologically inactive HIV-1 Nef mutant incorporating into EVs at quite high levels. Here, we analyze the immunogenic properties in human cells of EVs engineered with SARS-CoV-2 N fused at the C-terminus of either Nef^mut or a deletion mutant of Nef^mut referred to as Nef^mutPL. The analysis of in vitro-produced EVs has supported the uploading of N protein when fused with truncated Nef^mut. Mice injected with DNA vectors expressed each fusion protein developed robust SARS-CoV-2 N-specific CD8⁺ T cell immune responses. When ex vivo human dendritic cells were challenged with EVs engineered with either fusion products, the induction of a robust N-specific CTL activity, as evaluated by both CD107a and trogocytosis assays, was observed. Through these data we achieved the proof-of-principle that engineered EVs can be instrumental to elicit anti-SARS-CoV-2 CTL immune response in human cells. This achievement represents a mandatory step towards the upcoming experimentations in pre-clinical models focused on intranasal administration of N-engineered EVs. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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9 pages, 2714 KiB

Open AccessArticle

Vulnerability Predictors of Post-Vaccine SARS-CoV-2 Infection and Disease—Empirical Evidence from a Large Population-Based Italian Platform

by Giovanni Corrao, Matteo Franchi, Danilo Cereda, Francesco Bortolan, Olivia Leoni, Catia Rosanna Borriello, Petra Giulia Della Valle, Marcello Tirani, Giovanni Pavesi, Antonio Barone, Michele Ercolanoni, Jose Jara, Massimo Galli and Guido Bertolaso

Vaccines 2022, 10(6), 845; https://doi.org/10.3390/vaccines10060845 - 26 May 2022

Viewed by 1448

Abstract

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case–control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 [...] Read more.

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case–control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 January 2021 to 31 July 2021, and followed from 14 days after vaccine completion to 11 November 2021. Overall, 17,996 infections and 3023 severe illness cases occurred. For each case, controls were 1:1 (infection cases) or 1:10 (severe illness cases) matched for municipality of residence and date of vaccination completion. The association between selected predictors (sex, age, previous occurrence of SARS-CoV-2 infection, type of vaccine received, number of previous contacts with the Regional Health Service (RHS), and the presence of 59 diseases) and outcomes was assessed by using multivariable conditional logistic regression models. Sex, age, previous SARS-CoV-2 infection, type of vaccine and number of contacts with the RHS were associated with the risk of infection and severe illness. Moreover, higher odds of infection and severe illness were significantly associated with 14 and 34 diseases, respectively, among those investigated. These results can be helpful to clinicians and policy makers for prioritizing interventions. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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7 pages, 910 KiB

Open AccessArticle

Omicron Infection Evokes Cross-Protection against SARS-CoV-2 Variants in Vaccinees

by Gabriele Anichini, Chiara Terrosi, Claudia Gandolfo, Gianni Gori Savellini, Simonetta Fabrizi, Giovanni Battista Miceli, Federico Franchi and Maria Grazia Cusi

Vaccines 2022, 10(5), 808; https://doi.org/10.3390/vaccines10050808 - 19 May 2022

Cited by 6 | Viewed by 2055

Abstract

Due to the rapid global spread of the Omicron (B.1.1.529) variant, efforts to scale up COVID-19 booster vaccination have been improved, especially in light of the increasing evidence of reduced neutralizing antibody (NT Ab) over time in vaccinated subjects. In this study, neutralizing [...] Read more.

Due to the rapid global spread of the Omicron (B.1.1.529) variant, efforts to scale up COVID-19 booster vaccination have been improved, especially in light of the increasing evidence of reduced neutralizing antibody (NT Ab) over time in vaccinated subjects. In this study, neutralizing antibody responses against the Wild-Type, Delta, and Omicron strains were evaluated among vaccinees, both infected with Omicron or uninfected, and non-vaccinated subjects infected with Omicron. The aim of the study was to compare the cross-protective humoral response to the variant strains induced by vaccination and/or Omicron infection. The results showed a significant difference in the neutralizing antibody response between the vaccinees and the Omicron-infected vaccinated subjects against the three tested strains (p < 0.001), confirming the booster effect of the Omicron infection in the vaccinees. By contrast, Omicron infection only did not enhance the antibody response to the other variants, indicating a lack of cross-protection. These results suggest the importance of updating the current formulation of the SARS-CoV-2 vaccine to protect people against the Omicron subvariants. A specific Omicron vaccine, administered as a booster for the previously adopted mRNA vaccines, may protect against a wider range of SARS-CoV-2 variants. However, it is unlikely that the Omicron vaccine alone would be able to protect non-vaccinated subjects against other circulating variants. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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19 pages, 3286 KiB

Open AccessArticle

The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates

by Seung-Phil Shin, Kwang-Soo Shin, Jeong-Mi Lee, In-Kyung Jung, Jimo Koo, Seung-Woo Lee, Seowoo Park, Jieun Shin, Myunghwan Park, Bongju Park, Hanseul Oh, Bon-Sang Koo, Jungjoo Hong, Choong-Min Ryu, Jae-Ouk Kim, Taegwon Oh and Chang-Yuil Kang

Vaccines 2022, 10(5), 712; https://doi.org/10.3390/vaccines10050712 - 30 Apr 2022

Cited by 3 | Viewed by 2678

Abstract

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 [...] Read more.

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with a single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced T_h1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with a single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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7 pages, 1057 KiB

Open AccessCommunication

Comparable Post-Vaccination Decay of Neutralizing Antibody Response to Wild-Type and Delta SARS-CoV-2 Variant in Healthcare Workers Recovered from Mild or Asymptomatic Infection

by Ilaria Vicenti, Monica Basso, Filippo Dragoni, Francesca Gatti, Renzo Scaggiante, Lia Fiaschi, Saverio G. Parisi and Maurizio Zazzi

Vaccines 2022, 10(4), 580; https://doi.org/10.3390/vaccines10040580 - 09 Apr 2022

Cited by 1 | Viewed by 1635

Abstract

We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of 296 days) in immunocompetent healthcare [...] Read more.

We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of 296 days) in immunocompetent healthcare workers (HCWs). Live virus microneutralization against the B.1 and Delta SARS-CoV-2 variants was performed in VERO E6 cell cultures. The median NtAb titers for B.1 and Delta were comparable and highly correlated at both 20 and 200 days after the second vaccine dose in the 23 HCWs enrolled (median age, 46 years). A small group of naturally infected unvaccinated HCWs had comparable NtAb titers for the two strains after a median follow-up of 522 days from infection diagnosis. The NtAb response to the Delta VoC appears to follow the same long-term dynamics as the wild-type response regardless of the vaccinal boost; data collected after three antigen stimulations (natural infection followed by two doses of the BNT162b2 mRNA vaccine) may be helpful for tailoring the continuous monitoring of vaccine protection against SARS-CoV-2 variants over time. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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12 pages, 1081 KiB

Open AccessArticle

Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants

by Vladimir A. Gushchin, Inna V. Dolzhikova, Alexey M. Shchetinin, Alina S. Odintsova, Andrei E. Siniavin, Maria A. Nikiforova, Andrei A. Pochtovyi, Elena V. Shidlovskaya, Nadezhda A. Kuznetsova, Olga A. Burgasova, Liudmila V. Kolobukhina, Anna A. Iliukhina, Anna V. Kovyrshina, Andrey G. Botikov, Aleksandra V. Kuzina, Daria M. Grousova, Amir I. Tukhvatulin, Dmitry V. Shcheblyakov, Olga V. Zubkova, Oksana V. Karpova, Olga L. Voronina, Natalia N. Ryzhova, Ekaterina I. Aksenova, Marina S. Kunda, Dmitry A. Lioznov, Daria M. Danilenko, Andrey B. Komissarov, Artem P. Tkachuck, Denis Y. Logunov and Alexander L. Gintsburg Show full author list Hide full author list

Vaccines 2021, 9(7), 779; https://doi.org/10.3390/vaccines9070779 - 12 Jul 2021

Cited by 88 | Viewed by 107178

Abstract

Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are [...] Read more.

Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from “Sputnik V”-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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Review

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25 pages, 385 KiB

Open AccessReview

Challenges to Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Diseases

by Giuseppe A. Ramirez, Chiara Asperti, Valentina Cucca and Mona-Rita Yacoub

Vaccines 2021, 9(10), 1147; https://doi.org/10.3390/vaccines9101147 - 08 Oct 2021

Cited by 8 | Viewed by 2631

Abstract

Aberrant deployment of the immune response is a hallmark pathogenic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19), possibly accounting for high morbidity and mortality, especially in patients with comorbidities, including immune-mediated disorders. Immunisation with SARS-COV-2 vaccines successfully instructs the [...] Read more.

Aberrant deployment of the immune response is a hallmark pathogenic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19), possibly accounting for high morbidity and mortality, especially in patients with comorbidities, including immune-mediated disorders. Immunisation with SARS-COV-2 vaccines successfully instructs the immune system to limit viral spread into tissues, mitigate COVID-19 manifestations and prevent its most detrimental inflammatory complications in the general population. Patients with immune-mediated diseases have been excluded from vaccine registration trials, foreclosing the acquisition of specific efficacy and safety data. In this review, we aimed to summarise and critically discuss evidence from real-world studies addressing this issue to provide a comprehensive view of the impact of vaccination practices in patients with allergy, autoimmunity or immunodeficiency. We analysed clinical and laboratory data from 34 studies involving more than 13,000 subjects with various immune disorders who were vaccinated with mRNA- DNA- or inactivated viral particle-based vaccines. These data globally support the safe and effective use of SARS-CoV-2 vaccines in patients with immune-mediated diseases, although patient-tailored strategies to determine vaccination timing, vaccine choice and background therapy management are warranted to optimise vaccination outcomes. More data are needed regarding patients with primary immunodeficiencies. Full article

(This article belongs to the Special Issue Vaccine Candidate against SARS-CoV-2)

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