Vaccines

Editorial

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4 pages, 201 KiB

Open AccessEditorial

SARS-CoV-2 BA.2.86 (“Pirola”): Is it Pi or Just Another Omicron Sublineage?

by Daniele Focosi, Pietro Giorgio Spezia and Fabrizio Maggi

Vaccines 2023, 11(11), 1634; https://doi.org/10.3390/vaccines11111634 - 25 Oct 2023

Cited by 5 | Viewed by 2437

Abstract

The SARS-CoV-2 sublineage BA [...] Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

Research

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19 pages, 3589 KiB

Open AccessArticle

Immunogenicity and Protective Efficacy of Psoralen-Inactivated SARS-CoV-2 Vaccine in Nonhuman Primates

by John W. Sanders, Daniel Ewing, Appavu K. Sundaram, Christopher Scott Gamble, Maria Blevins, Zhaodong Liang, Leigh Ann Sanders, David A. Ornelles, Peifang Sun, Klara Lenart, Hendrik Feuerstein, Karin Loré, Nikolai Petrovsky, Maya Williams and Kevin R. Porter

Vaccines 2024, 12(5), 451; https://doi.org/10.3390/vaccines12050451 - 24 Apr 2024

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Abstract

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted public health and the economy worldwide. Most of the currently licensed COVID-19 vaccines act by inhibiting the receptor-binding function of the SARS-CoV-2 spike protein. The constant emergence of SARS-CoV-2 variants [...] Read more.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted public health and the economy worldwide. Most of the currently licensed COVID-19 vaccines act by inhibiting the receptor-binding function of the SARS-CoV-2 spike protein. The constant emergence of SARS-CoV-2 variants resulting from mutations in the receptor-binding domain (RBD) leads to vaccine immune evasion and underscores the importance of broadly acting COVID-19 vaccines. Inactivated whole virus vaccines can elicit broader immune responses to multiple epitopes of several antigens and help overcome such immune evasions. We prepared a psoralen-inactivated SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) and evaluated its immunogenicity and efficacy in nonhuman primates (NHPs) when administered with the Advax-CpG adjuvant. We also evaluated the SARS-CoV-2 PsIV as a booster shot in animals vaccinated with a DNA vaccine that can express the full-length spike protein. The Advax-CpG-adjuvanted SARS-CoV-2 PsIV elicited a dose-dependent neutralizing antibody response in the NHPs, as measured using a serum microneutralization assay against the SARS-CoV-2 Washington strain and the Delta variant. The animals vaccinated with the DNA vaccine followed by a boosting dose of the SARS-CoV-2 PsIV exhibited the highest neutralizing antibody responses and were able to quickly clear infection after an intranasal challenge with the SARS-CoV-2 Delta variant. Overall, the data show that the Advax-CpG-adjuvanted SARS-CoV-2 PsIV, either by itself or as a booster shot following nucleic acid (NA) vaccines, has the potential to protect against emerging variants. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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16 pages, 7494 KiB

Open AccessArticle

Development of a Candidate TMV Epitope Display Vaccine against SARS-CoV-2

by Kelvin Phiri and Larry Grill

Vaccines 2024, 12(5), 448; https://doi.org/10.3390/vaccines12050448 - 23 Apr 2024

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Abstract

Essential in halting the COVID-19 pandemic caused by SARS-CoV-2, it is crucial to have stable, effective, and easy-to-manufacture vaccines. We developed a potential vaccine using a tobacco mosaic virus (TMV) epitope display model presenting peptides derived from the SARS-CoV-2 spike protein. The TMV-epitope [...] Read more.

Essential in halting the COVID-19 pandemic caused by SARS-CoV-2, it is crucial to have stable, effective, and easy-to-manufacture vaccines. We developed a potential vaccine using a tobacco mosaic virus (TMV) epitope display model presenting peptides derived from the SARS-CoV-2 spike protein. The TMV-epitope fusions in laboratory tests demonstrated binding to the SARS-CoV-2 polyclonal antibodies. The fusion constructs maintained critical epitopes of the SARS-CoV-2 spike protein, and two in particular spanned regions of the receptor-binding domain that have mutated in the more recent SARS-CoV-2 variants. This would allow for the rapid modification of vaccines in response to changes in circulating variants. The TMV-peptide fusion constructs also remained stable for over 28 days when stored at temperatures between −20 and 37 °C, an ideal property when targeting developing countries. Immunogenicity studies conducted on BALB/c mice elicited robust antibody responses against SARS-CoV-2. A strong IFNγ response was also observed in immunized mice. Three of the six TMV-peptide fusion constructs produced virus-neutralizing titers, as measured with a pseudovirus neutralization assay. These TMV-peptide fusion constructs can be combined to make a multivalent vaccine that could be adapted to meet changing virus variants. These findings demonstrate the development of a stable COVID-19 vaccine candidate by combining SARS-CoV-2 spike protein-derived peptides presented on the surface of a TMV nanoparticle. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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15 pages, 1190 KiB

Open AccessArticle

Immunogenicity and Safety of Half-Dose Heterologous mRNA-1273 Booster Vaccination for Adults Primed with the CoronaVac^® and ChAdOx1-S Vaccines for SARS-CoV-2

by Nina Dwi Putri, Aqila Sakina Zhafira, Pratama Wicaksana, Robert Sinto, Gryselda Hanafi, Lowilius Wiyono, Ari Prayitno, Mulya Rahma Karyanti, Murni Luciana Naibaho, Febrina Febrina, Hadyana Sukandar, Vivi Setiawaty, Mursinah Mursinah, Ahmat Rediansya Putra, Heri Wibowo, Julitasari Sundoro, Hindra Irawan Satari, Dwi Oktavia, Pretty Multihartina, Dante Saksono Harbuwono and Sri Rezeki Hadinegoro Show full author list Hide full author list

Vaccines 2024, 12(4), 344; https://doi.org/10.3390/vaccines12040344 - 22 Mar 2024

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Abstract

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational [...] Read more.

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac^® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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13 pages, 1455 KiB

Open AccessArticle

RBD-Protein/Peptide Vaccine UB-612 Elicits Mucosal and Fc-Mediated Antibody Responses against SARS-CoV-2 in Cynomolgus Macaques

by Shixia Wang, Farshad Guirakhoo, Sivakumar Periasamy, Valorie Ryan, Jonathan Wiggins, Chandru Subramani, Brett Thibodeaux, Jaya Sahni, Michael Hellerstein, Natalia A. Kuzmina, Alexander Bukreyev, Jean-Cosme Dodart and Alexander Rumyantsev

Vaccines 2024, 12(1), 40; https://doi.org/10.3390/vaccines12010040 - 29 Dec 2023

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Abstract

Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein–peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate [...] Read more.

Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein–peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and antibody-dependent NK cell activation (ADNKA) assays. In cynomolgus macaques, UB-612 induced potent serum-neutralizing, RBD-specific IgG binding, ACE2 binding-inhibition antibodies, and antibodies with Fc-mediated effector functions in ADMP and ADNKA assays. Additionally, immunized animals developed mucosal antibodies in bronchoalveolar lavage fluids (BAL). The level of mucosal or serum ADMP and ADNKA antibodies was found to be UB-612 dose-dependent. Our results highlight that the novel subunit UB-612 vaccine is a potent B-cell immunogen inducing polyfunctional antibody responses contributing to anti-viral immunity and vaccine efficacy. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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18 pages, 1965 KiB

Open AccessArticle

A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2

by Takenao Koseki, Mayumi Teramachi, Minako Koga, Minoru S. H. Ko, Tomokazu Amano, Hong Yu, Misa Amano, Erica Leyder, Maria Badiola, Priyanka Ray, Jiyoung Kim, Akihiro C. Ko, Achouak Achour, Nan-ping Weng, Takumi Imai, Hisako Yoshida, Satsuki Taniuchi, Ayumi Shintani, Hidetsugu Fujigaki, Masashi Kondo and Yohei Doi Show full author list Hide full author list

Vaccines 2023, 11(12), 1767; https://doi.org/10.3390/vaccines11121767 - 27 Nov 2023

Viewed by 1343

Abstract

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a key role in reducing morbidity and mortality from coronavirus disease 2019 (COVID-19). We conducted a double-blind, placebo-controlled phase I/II trial to evaluate the safety, tolerability, and immunogenicity of EXG-5003, a [...] Read more.

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a key role in reducing morbidity and mortality from coronavirus disease 2019 (COVID-19). We conducted a double-blind, placebo-controlled phase I/II trial to evaluate the safety, tolerability, and immunogenicity of EXG-5003, a two-dose, controllable self-replicating RNA vaccine against SARS-CoV-2. EXG-5003 encodes the receptor binding domain (RBD) of SARS-CoV-2 and was administered intradermally without lipid nanoparticles (LNPs). The participants were followed for 12 months. Forty healthy participants were enrolled in Cohort 1 (5 µg per dose, n = 16; placebo, n = 4) and Cohort 2 (25 µg per dose, n = 16; placebo, n = 4). No safety concerns were observed with EXG-5003 administration. SARS-CoV-2 RBD antibody titers and neutralizing antibody titers were not elevated in either cohort. Elicitation of antigen-specific cellular immunity was observed in the EXG-5003 recipients in Cohort 2. At the 12-month follow-up, participants who had received an approved mRNA vaccine (BNT162b2 or mRNA-1273) >1 month after receiving the second dose of EXG-5003 showed higher cellular responses compared with equivalently vaccinated participants in the placebo group. The findings suggest a priming effect of EXG-5003 on the long-term cellular immunity of approved SARS-CoV-2 mRNA vaccines. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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12 pages, 1363 KiB

Open AccessArticle

Torquetenovirus Loads in Peripheral Blood Predict Both the Humoral and Cell-Mediated Responses to SARS-CoV-2 Elicited by the mRNA Vaccine in Liver Transplant Recipients

by Claudia Minosse, Giulia Matusali, Silvia Meschi, Germana Grassi, Massimo Francalancia, Gianpiero D’Offizi, Pietro Giorgio Spezia, Anna Rosa Garbuglia, Marzia Montalbano, Daniele Focosi, Enrico Girardi, Francesco Vaia, Giuseppe Maria Ettorre and Fabrizio Maggi

Vaccines 2023, 11(11), 1656; https://doi.org/10.3390/vaccines11111656 - 28 Oct 2023

Viewed by 1014

Abstract

Three years into the COVID-19 pandemic, mass vaccination campaigns have largely controlled the disease burden but have not prevented virus circulation. Unfortunately, many immunocompromised patients have failed to mount protective immune responses after repeated vaccinations, and liver transplant recipients are no exception. Across [...] Read more.

Three years into the COVID-19 pandemic, mass vaccination campaigns have largely controlled the disease burden but have not prevented virus circulation. Unfortunately, many immunocompromised patients have failed to mount protective immune responses after repeated vaccinations, and liver transplant recipients are no exception. Across different solid organ transplant populations, the plasma levels of Torquetenovirus (TTV), an orphan and ubiquitous human virus under control of the immune system, have been shown to predict the antibody response after COVID-19 vaccinations. We show here a single-institution experience with TTV viremia in 134 liver transplant recipients at their first or third dose. We found that TTV viremia before the first and third vaccine doses predicts serum anti-SARS-CoV-2 Spike receptor-binding domain (RBD) IgG levels measured 2–4 weeks after the second or third dose. Pre-vaccine TTV loads were also associated with peripheral blood anti-SARS-CoV-2 cell-mediated immunity but not with serum SARS-CoV-2 neutralizing antibody titers. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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19 pages, 11860 KiB

Open AccessArticle

Analysing the In-Use Stability of mRNA-LNP COVID-19 Vaccines Comirnaty™ (Pfizer) and Spikevax™ (Moderna): A Comparative Study of the Particulate

by Jesús Hermosilla, Airan Alonso-García, Antonio Salmerón-García, José Cabeza-Barrera, Antonio L. Medina-Castillo, Raquel Pérez-Robles and Natalia Navas

Vaccines 2023, 11(11), 1635; https://doi.org/10.3390/vaccines11111635 - 25 Oct 2023

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Abstract

Comirnaty™ and Spikevax™ were the first vaccines approved for human use based on modified non-replicating mRNA lipophilic nanoparticle (mRNA-LNP) technology, with great success in the treatment of COVID-19. They have been used massively worldwide. One of the major inconveniences of these vaccines is [...] Read more.

Comirnaty™ and Spikevax™ were the first vaccines approved for human use based on modified non-replicating mRNA lipophilic nanoparticle (mRNA-LNP) technology, with great success in the treatment of COVID-19. They have been used massively worldwide. One of the major inconveniences of these vaccines is related to pharmaceutical stability issues. Proper transportation, storage, and in-use handling before administration to patients are critical steps since failures can potentially reduce potency. In this research, the in-use stability of Comirnaty™ and Spikevax™ clinical samples was analysed and the results were compared. As changes in the size of the mRNA-LNPs are related to potency, these modifications were analysed by qualitative Dynamic Light Scattering (DLS) as a stability-indicating method for control and stressed vaccine samples. Strong stress factors (accelerated light irradiation, manual shaking, and vortex vibration) and conditions that mimic in-use handling (exposure to natural light and room temperature, repeated cycles of injections, and 24 h storage in syringes) were checked. The morphology of the mRNA-LNPs was analysed by Transmission Electron Microscopy (TEM) to better interpret and support the DLS results. Although the two vaccines are based on the same mRNA-LNP technology, the results demonstrate that they are characterised by very different particle size profiles and behaviours against different handling/stress conditions. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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14 pages, 631 KiB

Open AccessArticle

Antibiotic Use Prior to COVID-19 Vaccine Is Associated with Higher Risk of COVID-19 and Adverse Outcomes: A Propensity-Scored Matched Territory-Wide Cohort

by Ka Shing Cheung, Vincent K. C. Yan, Lok Ka Lam, Xuxiao Ye, Ivan F. N. Hung, Esther W. Chan and Wai K. Leung

Vaccines 2023, 11(8), 1341; https://doi.org/10.3390/vaccines11081341 - 08 Aug 2023

Cited by 3 | Viewed by 1263

Abstract

Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged [...] Read more.

Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. Results: Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2–16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14–1.19), hospitalization (aIRR: 1.75;95% CI: 1.65–1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21–2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18–2.22 and aIRR: 2.70, 95% CI: 1.54–4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Conclusions: Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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Review

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15 pages, 643 KiB

Open AccessReview

COVID-19 Vaccination and Immunosuppressive Therapy in Immune-Mediated Inflammatory Diseases

by José M. Serra López-Matencio, Esther F. Vicente-Rabaneda, Estefanía Alañón, Ainhoa Aranguren Oyarzabal, Pedro Martínez Fleta and Santos Castañeda

Vaccines 2023, 11(12), 1813; https://doi.org/10.3390/vaccines11121813 - 04 Dec 2023

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Abstract

The COVID-19 vaccination program has probably been the most complex and extensive project in history until now, which has been a challenge for all the people involved in the planning and management of this program. Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive [...] Read more.

The COVID-19 vaccination program has probably been the most complex and extensive project in history until now, which has been a challenge for all the people involved in the planning and management of this program. Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy have required special attention, not only because of the particular haste in carrying out the process but also because of the uncertainty regarding their response to the vaccines. We now have strong scientific evidence that supports the hypothesis that immunosuppressive therapy inhibits the humoral response to vaccines against other infectious agents, such as influenza, pneumococcus and hepatitis B. This has led to the hypothesis that the same could happen with the COVID-19 vaccine. Several studies have therefore already been carried out in this area, suggesting that temporarily discontinuing the administration of methotrexate for 2 weeks post-vaccination could improve the vaccine response, and other studies with various immunosuppressive drugs are in the same line. However, the fact of withholding or interrupting immunosuppressive therapy when dealing with COVID-19 vaccination remains unclear. On this basis, our article tries to compile the information available on the effect of immunosuppressant agents on COVID-19 vaccine responses in patients with IMIDs and proposes an algorithm for the management of these patients. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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