Research

17 pages, 5885 KiB

Open AccessArticle

Large-Scale Purification and Characterization of Recombinant Receptor-Binding Domain (RBD) of SARS-CoV-2 Spike Protein Expressed in Yeast

by Gaurav Nagar, Siddharth Jain, Meghraj Rajurkar, Rakesh Lothe, Harish Rao, Sourav Majumdar, Manish Gautam, Sergio A. Rodriguez-Aponte, Laura E. Crowell, J. Christopher Love, Prajakta Dandekar, Amita Puranik, Sunil Gairola, Umesh Shaligram and Ratnesh Jain

Vaccines 2023, 11(10), 1602; https://doi.org/10.3390/vaccines11101602 - 16 Oct 2023

Viewed by 1878

Abstract

SARS-CoV-2 spike protein is an essential component of numerous protein-based vaccines for COVID-19. The receptor-binding domain of this spike protein is a promising antigen with ease of expression in microbial hosts and scalability at comparatively low production costs. This study describes the production, [...] Read more.

SARS-CoV-2 spike protein is an essential component of numerous protein-based vaccines for COVID-19. The receptor-binding domain of this spike protein is a promising antigen with ease of expression in microbial hosts and scalability at comparatively low production costs. This study describes the production, purification, and characterization of RBD of SARS-CoV-2 protein, which is currently in clinical trials, from a commercialization perspective. The protein was expressed in Pichia pastoris in a large-scale bioreactor of 1200 L capacity. Protein capture and purification are conducted through mixed-mode chromatography followed by hydrophobic interaction chromatography. This two-step purification process produced RBD with an overall productivity of ~21 mg/L at >99% purity. The protein’s primary, secondary, and tertiary structures were also verified using LCMS-based peptide mapping, circular dichroism, and fluorescence spectroscopy, respectively. The glycoprotein was further characterized for quality attributes such as glycosylation, molecular weight, purity, di-sulfide bonding, etc. Through structural analysis, it was confirmed that the product maintained a consistent quality across different batches during the large-scale production process. The binding capacity of RBD of spike protein was also assessed using human angiotensin-converting enzyme 2 receptor. A low binding constant range of KD values, ranging between 3.63 × 10⁻⁸ to 6.67 × 10⁻⁸, demonstrated a high affinity for the ACE2 receptor, revealing this protein as a promising candidate to prevent the entry of COVID-19 virus. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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17 pages, 9673 KiB

Open AccessArticle

Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants

by Michael J. Moser, Lindsay Hill-Batorski, Richard A. Bowen, Sarah M. Matejka, David Marshall, Yoshihiro Kawaoka, Gabriele Neumann and Pamuk Bilsel

Vaccines 2023, 11(6), 1063; https://doi.org/10.3390/vaccines11061063 - 05 Jun 2023

Cited by 2 | Viewed by 2114

Abstract

Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of [...] Read more.

Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, which are considered to be sufficient to protect against viral infection. Moreover, SARS-CoV-2 M2SR elicited cross-reactive serum and mucosal antibodies to the Omicron BA.4/BA.5 variant. The SARS-CoV-2 M2SR vaccine also maintained strong immune responses to influenza A with high titers of anti H3 serum IgG and hemagglutination inhibition (HAI) antibody titers corresponding to those seen from the control M2SR vector alone. With a proven safety record and robust immunological profile in humans that includes mucosal immunity, the M2SR influenza viral vector expressing key SARS-CoV-2 antigens could provide more efficient protection against influenza and SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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14 pages, 901 KiB

Open AccessArticle

Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan

by Yuta Tani, Morihito Takita, Yurie Kobashi, Masatoshi Wakui, Tianchen Zhao, Chika Yamamoto, Hiroaki Saito, Moe Kawashima, Sota Sugiura, Yoshitaka Nishikawa, Fumiya Omata, Yuzo Shimazu, Takeshi Kawamura, Akira Sugiyama, Aya Nakayama, Yudai Kaneko, Tetsuhiko Kodama, Masahiro Kami and Masaharu Tsubokura

Vaccines 2023, 11(5), 920; https://doi.org/10.3390/vaccines11050920 - 29 Apr 2023

Cited by 4 | Viewed by 2073

Abstract

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima [...] Read more.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19–2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19–3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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20 pages, 4387 KiB

Open AccessArticle

Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell^®

by Sevastyan O. Rabdano, Ellina A. Ruzanova, Iuliia V. Pletyukhina, Nikita S. Saveliev, Kirill L. Kryshen, Anastasiia E. Katelnikova, Petr P. Beltyukov, Liliya N. Fakhretdinova, Ariana S. Safi, German O. Rudakov, Sergei A. Arakelov, Igor V. Andreev, Ilya A. Kofiadi, Musa R. Khaitov, Rudolf Valenta, Daria S. Kryuchko, Igor A. Berzin, Natalia S. Belozerova, Anatoly E. Evtushenko, Viktor P. Truhin and Veronika I. Skvortsova Show full author list Hide full author list

Vaccines 2023, 11(4), 874; https://doi.org/10.3390/vaccines11040874 - 20 Apr 2023

Cited by 5 | Viewed by 2445

Abstract

The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to [...] Read more.

The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4⁺/CD8⁺ T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell^® thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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12 pages, 1574 KiB

Open AccessArticle

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults

by Ruiqi Zhang, Kwok-Hung Chan, Pui Wang, Runhong Zhou, Henry Kwong-Chi Yau, Creany Ka-Wai Wong, Meena Wai-Lam Au, Anthony Raymond Tam, Chi-Tao Ng, Matthew Kwok-Chung Lou, Na Liu, Haode Huang, Shaofeng Deng, Rachel Chun-Yee Tam, Ying Liu, Teng Long, Hoi-Wah Tsoi, Miko K. W. Ng, Jian-Piao Cai, Kelvin Kai-Wang To, Man-Fung Yuen, Zhiwei Chen, Honglin Chen, Kwok-Yung Yuen and Ivan Fan-Ngai Hung Show full author list Hide full author list

Vaccines 2023, 11(4), 723; https://doi.org/10.3390/vaccines11040723 - 24 Mar 2023

Cited by 3 | Viewed by 1791

Abstract

An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18–55 and COVID-19 vaccines naïve, between [...] Read more.

An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18–55 and COVID-19 vaccines naïve, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 × 10⁷ EID₅₀/ dose and 1 × 10^7.7 EID₅₀/ dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events (p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/10⁶ PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/10⁶ PBMC (day 42) from 2.5 SFU/10⁶ PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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10 pages, 1373 KiB

Open AccessArticle

Screening of Efficient Adjuvants for the RBD-Based Subunit Vaccine of SARS-CoV-2

by Juan Shi, Yu Zhao, Min Peng, Suyue Zhu, Yandan Wu, Ruixue Ji and Chuanlai Shen

Vaccines 2023, 11(4), 713; https://doi.org/10.3390/vaccines11040713 - 23 Mar 2023

Cited by 3 | Viewed by 1669

Abstract

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more transmissible, with a reduced sensitivity to vaccines targeting the original virus strain. Therefore, developing an effective vaccine against both the original SARS-CoV-2 strain and its variants is an urgent need. It [...] Read more.

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more transmissible, with a reduced sensitivity to vaccines targeting the original virus strain. Therefore, developing an effective vaccine against both the original SARS-CoV-2 strain and its variants is an urgent need. It is known that the receptor-binding domain (RBD) in the S protein of SARS-CoV-2 is an important vaccine target, but subunit vaccines usually have lower immunogenicity and efficacy. Thus, selecting appropriate adjuvants to enhance the immunogenicity of protein-based subunit vaccine antigens is necessary. Here, an RBD-Fc subunit vaccine of SARS-CoV-2 has been generated, followed by vaccination in B6 mice, and four adjuvant regimens were investigated, including aluminum salts (Alum) + 3-O-desacyl-4′-monophosphoryl lipid A (MPL), AddaVax, QS21 + MPL, and Imiquimod. The adjuvant potency was evaluated by comparing the elicited polyclonal antibodies titers with measuring binding to RBD and S protein in ELISA and Western blot analysis, and also the cross-neutralizing antibodies titers using a pseudovirus infection assay of hACE2-expressing 293T cells, with pseudoviruses expressing the S protein of the SARS-CoV-2 original strain and Delta strain. The presence of QS21 + MPL adjuvant induced stronger polyclonal antibody response and neutralization potency blocking the original strain and Delta strain, as compared with the non-adjuvant RBD-Fc group and other adjuvant groups. Meanwhile, Imiquimod even had a negative effect in inducing specific antibodies and cross-neutralizing antibody production as an adjuvant. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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9 pages, 641 KiB

Open AccessArticle

Assessment of Reactivity to the Administration of the mRNA Vaccine after Six Months of Observation

by Sebastian Slomka, Patrycja Zieba, Oskar Rosiak and Anna Piekarska

Vaccines 2023, 11(2), 366; https://doi.org/10.3390/vaccines11020366 - 06 Feb 2023

Cited by 1 | Viewed by 1464

Abstract

Background: The fast spread of the SARS-CoV-2 virus accelerated efforts to create an effective vaccine, and a novel mRNA vaccine was the first to appear effective. Scientific evidence regarding mRNA vaccination is limited; therefore, understanding how the immune system responds to an mRNA [...] Read more.

Background: The fast spread of the SARS-CoV-2 virus accelerated efforts to create an effective vaccine, and a novel mRNA vaccine was the first to appear effective. Scientific evidence regarding mRNA vaccination is limited; therefore, understanding how the immune system responds to an mRNA vaccine is critical. Our study was aimed at a long-term analysis of the presence and maintenance of the immune response using the chemiluminescent method by analyzing the level of IgG antibodies in vaccinated people who were and were not infected with the SARS-CoV-2 virus. Materials and methods: Healthcare workers with a history of COVID-19 or who were naïve to the infection were recruited for this study and administered two subsequent doses of the Comirnaty vaccine. IgG SRBD antibody levels were evaluated every month for six consecutive months using the chemiluminescent immunoassay (CLIA). Results: A total of 149 individuals were recruited for this study, 68 had evidence of past COVID-19 infection, with 63 exhibiting elevated IgG SRBD antibody levels at initial evaluation. Statistically significant differences were observed between COVID-19 convalescents and non-convalescents at all study time points, with the convalescent group consequently representing higher antibody levels. Conclusions: COVID-19 convalescents showed a stronger immune response to the vaccine after the first dose. This group exhibited higher IgG levels in all examinations during the observation period. The natural waning of antibody levels can be observed within six months. A booster vaccination may be required. No serious side effects were observed. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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23 pages, 4235 KiB

Open AccessArticle

Full-Lung Prophylaxis against SARS-CoV-2 by One-Shot or Booster Intranasal Lentiviral Vaccination in Syrian Golden Hamsters

by Benjamin Vesin, Pierre Authié, Catherine Blanc, Ingrid Fert, Amandine Noirat, Fabien Le Chevalier, Yu Wei, Min-Wen Ku, Kirill Nemirov, François Anna, David Hardy, Cyril Planchais, Hugo Mouquet, Françoise Guinet, Pierre Charneau, Laleh Majlessi and Maryline Bourgine

Vaccines 2023, 11(1), 12; https://doi.org/10.3390/vaccines11010012 - 21 Dec 2022

Cited by 1 | Viewed by 1557

Abstract

Following the breakthrough of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in recent months and the incomplete efficiency of the currently available vaccines, development of more effective vaccines is desirable. Non-integrative, non-cytopathic and non-inflammatory lentiviral vectors elicit sterilizing prophylaxis against SARS-CoV-2 [...] Read more.

Following the breakthrough of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in recent months and the incomplete efficiency of the currently available vaccines, development of more effective vaccines is desirable. Non-integrative, non-cytopathic and non-inflammatory lentiviral vectors elicit sterilizing prophylaxis against SARS-CoV-2 in preclinical animal models and are particularly suitable for mucosal vaccination, which is acknowledged as the most effective in reducing viral transmission. Here, we demonstrate that a single intranasal administration of a vaccinal lentiviral vector encoding a stabilized form of the original SARS-CoV-2 Spike glycoprotein induces full-lung protection of respiratory tracts and strongly reduces pulmonary inflammation in the susceptible Syrian golden hamster model against the prototype SARS-CoV-2. In addition, we show that a lentiviral vector encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::S_Beta-2P) prevents pathology and reduces infectious viral loads in lungs and nasal turbinates following inoculation with the SARS-CoV-2 Omicron variant. Importantly, an intranasal boost with LV::S_Beta-2P improves cross-seroneutralization much better in LV::S_Beta-2P-primed hamsters than in their counterparts primed with an LV-encoding Spike from the ancestral SARS-CoV-2. These results strongly suggest that an immune imprint with the original Spike sequence has a negative impact on cross-protection against new variants. Our results tackle the issue of vaccine effectiveness in people who have already been vaccinated and have vanished immunity and indicate the efficiency of LV-based intranasal vaccination, either as a single dose or as booster. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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15 pages, 2142 KiB

Open AccessCommunication

Intradermal Immunization of SARS-CoV-2 Original Strain Trimeric Spike Protein Associated to CpG and AddaS03 Adjuvants, but Not MPL, Provide Strong Humoral and Cellular Response in Mice

by Luan Firmino-Cruz, Júlio Souza dos-Santos, Alessandra Marcia da Fonseca-Martins, Diogo Oliveira-Maciel, Gustavo Guadagnini-Perez, Victor A. Roncaglia-Pereira, Carlos H. Dumard, Francisca H. Guedes-da-Silva, Ana C. Vicente Santos, Renata G. F. Alvim, Tulio M. Lima, Federico F. Marsili, Daniel P. B. Abreu, Bartira Rossi-Bergmann, Andre M. Vale, Alessandra D’Almeida Filardy, Jerson Lima Silva, Andrea Cheble de Oliveira, Andre M. O. Gomes and Herbert Leonel de Matos Guedes

Vaccines 2022, 10(8), 1305; https://doi.org/10.3390/vaccines10081305 - 12 Aug 2022

Cited by 3 | Viewed by 2209

Abstract

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust [...] Read more.

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4⁺ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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13 pages, 3065 KiB

Open AccessArticle

Alum/CpG Adjuvanted Inactivated COVID-19 Vaccine with Protective Efficacy against SARS-CoV-2 and Variants

by Yuntao Zhang, Xiaotong Zheng, Wang Sheng, Hongyang Liang, Yuxiu Zhao, Xiujuan Zhu, Rong Yang, Yadan Zhang, Xiaofei Dong, Weidong Li, Fei Pei, Ling Ding, Zhen Chang, Li Deng, Guangying Yuan, Zhaona Yang, Di Zhu, Xiaoming Yang and Hui Wang

Vaccines 2022, 10(8), 1208; https://doi.org/10.3390/vaccines10081208 - 29 Jul 2022

Cited by 6 | Viewed by 2007

Abstract

Since the beginning of the COVID-19 pandemic, numerous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, including five variants of concern (VOC) strains listed by the WHO: Alpha, Beta, Gamma, Delta and Omicron. Extensive studies have shown that most of [...] Read more.

Since the beginning of the COVID-19 pandemic, numerous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, including five variants of concern (VOC) strains listed by the WHO: Alpha, Beta, Gamma, Delta and Omicron. Extensive studies have shown that most of these VOC strains, especially the currently dominant variant Omicron, can escape the host immune response induced by existing COVID-19 vaccines to different extents, which poses considerable risk to the health of human beings around the world. In the present study, we developed a vaccine based on inactivated SARS-CoV-2 and an adjuvant consisting of aluminum hydroxide (alum) and CpG. The immunogenicity and safety of the vaccine were investigated in rats. The candidate vaccine elicited high titers of SARS-CoV-2-spike-specific IgG antibody and neutralizing antibody in immunized rats, which not only neutralize the original SARS-CoV-2, but also showed great cross-neutralization activity against the Beta, Delta and Omicron variants. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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13 pages, 4464 KiB

Open AccessArticle

Vaccination with Omicron Inactivated Vaccine in Pre-vaccinated Mice Protects against SARS-CoV-2 Prototype and Omicron Variants

by Yuntao Zhang, Wenjie Tan, Zhiyong Lou, Yuxiu Zhao, Jin Zhang, Hongyang Liang, Na Li, Xiujuan Zhu, Ling Ding, Baoying Huang, Weimin Zhou, Yancen Guo, Zhaona Yang, Yuling Qiao, Zhenyu He, Bo Ma, Yao He, Di Zhu, Zhanhui Wang, Zhen Chang, Xue Zhao, Wei Wang, Ying Xu, Huiqin Zhu, Xiaotong Zheng, Chenlong Wang, Guangxue Xu, Guizhen Wu, Hui Wang and Xiaoming Yang Show full author list Hide full author list

Vaccines 2022, 10(7), 1149; https://doi.org/10.3390/vaccines10071149 - 19 Jul 2022

Cited by 8 | Viewed by 2279

Abstract

In response to the fast-waning immune response and the great threat of the Omicron variant of concern (VOC) to the public, we report the pilot-scale production of an inactivated Omicron vaccine candidate that induces high levels of neutralizing antibody titers to protect against [...] Read more.

In response to the fast-waning immune response and the great threat of the Omicron variant of concern (VOC) to the public, we report the pilot-scale production of an inactivated Omicron vaccine candidate that induces high levels of neutralizing antibody titers to protect against the Omicron virus. Here, we demonstrate that the inactivated Omicron vaccine is safe and effective in recalling immune responses to the HB02, Omicron, and Delta viruses after one or two doses of BBIBP-CorV. In addition, the efficient productivity and good genetic stability of the manufactured inactivated vaccine is proved. These results support the further evaluation of the Omicron vaccine in a clinical trial. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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12 pages, 2105 KiB

Open AccessArticle

Immunogenicity Evaluating of the Multivalent COVID-19 Inactivated Vaccine against the SARS-CoV-2 Variants

by Yuntao Zhang, Wenjie Tan, Zhiyong Lou, Baoying Huang, Weimin Zhou, Yuxiu Zhao, Jin Zhang, Hongyang Liang, Na Li, Xiujuan Zhu, Ling Ding, Yancen Guo, Zhenyu He, Yao He, Zhanhui Wang, Bo Ma, Meng Ma, Suhua Zhao, Zhen Chang, Xue Zhao, Xiaotong Zheng, Guizhen Wu, Hui Wang and Xiaoming Yang Show full author list Hide full author list

Vaccines 2022, 10(6), 956; https://doi.org/10.3390/vaccines10060956 - 16 Jun 2022

Cited by 8 | Viewed by 2348

Abstract

It has been reported that the novel coronavirus (COVID-19) has caused more than 286 million cases and 5.4 million deaths to date. Several strategies have been implemented globally, such as social distancing and the development of the vaccines. Several severe acute respiratory syndrome [...] Read more.

It has been reported that the novel coronavirus (COVID-19) has caused more than 286 million cases and 5.4 million deaths to date. Several strategies have been implemented globally, such as social distancing and the development of the vaccines. Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have appeared, such as Alpha, Beta, Gamma, Delta, and Omicron. With the rapid spread of the novel coronavirus and the rapidly changing mutants, the development of a broad-spectrum multivalent vaccine is considered to be the most effective way to defend against the constantly mutating virus. Here, we evaluated the immunogenicity of the multivalent COVID-19 inactivated vaccine. Mice were immunized by multivalent COVID-19 inactivated vaccine, and the neutralizing antibodies in serum were analyzed. The results show that HB02 + Delta + Omicron trivalent vaccine could provide broad spectrum protection against HB02, Beta, Delta, and Omicron virus. Additionally, the different multivalent COVID-19 inactivated vaccines could enhance cellular immunity. Together, our findings suggest that the multivalent COVID-19 inactivated vaccine can provide broad spectrum protection against HB02 and other virus variants in humoral and cellular immunity, providing new ideas for the development of a broad-spectrum COVID-19 vaccine. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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7 pages, 1229 KiB

Open AccessArticle

Methodology of Purification of Inactivated Cell-Culture-Grown SARS-CoV-2 Using Size-Exclusion Chromatography

by Anastasia A. Kovpak, Anastasia N. Piniaeva, Oleg A. Gerasimov, Irina O. Tcelykh, Mayya Y. Ermakova, Anna N. Zyrina, Dmitry V. Danilov, Yury Y. Ivin, Liubov I. Kozlovskaya and Aydar A. Ishmukhametov

Vaccines 2022, 10(6), 949; https://doi.org/10.3390/vaccines10060949 - 15 Jun 2022

Viewed by 2256

Abstract

Various types of COVID-19 vaccines, including adenovirus, mRNA, and inactivated ones, have been developed and approved for clinical use worldwide. Inactivated vaccines are produced using a proven technology that is widely used for the production of vaccines for the prevention and control of [...] Read more.

Various types of COVID-19 vaccines, including adenovirus, mRNA, and inactivated ones, have been developed and approved for clinical use worldwide. Inactivated vaccines are produced using a proven technology that is widely used for the production of vaccines for the prevention and control of infectious diseases, including influenza and poliomyelitis. The development of inactivated whole-virion vaccines commonly includes several stages: the production of cellular and viral biomass in cell culture; inactivation of the virus; filtration and ultrafiltration; chromatographic purification of the viral antigen; and formulation with stabilizers and adjuvants. In this study, the suitability of four resins for Size-Exclusion Chromatography was investigated for the purification of a viral antigen for the human COVID-19 vaccine. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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13 pages, 1366 KiB

Open AccessCommunication

Major Complex Trait for Early De Novo Programming ‘CoV-MAC-TED’ Detected in Human Nasal Epithelial Cells Infected by Two SARS-CoV-2 Variants Is Promising to Help in Designing Therapeutic Strategies

by José Hélio Costa, Shahid Aziz, Carlos Noceda and Birgit Arnholdt-Schmitt

Vaccines 2021, 9(12), 1399; https://doi.org/10.3390/vaccines9121399 - 26 Nov 2021

Cited by 4 | Viewed by 2443

Abstract

Background: Early metabolic reorganization was only recently recognized as an essentially integrated part of immunology. In this context, unbalanced ROS/RNS levels connected to increased aerobic fermentation, which is linked to alpha-tubulin-based cell restructuring and control of cell cycle progression, were identified as a [...] Read more.

Background: Early metabolic reorganization was only recently recognized as an essentially integrated part of immunology. In this context, unbalanced ROS/RNS levels connected to increased aerobic fermentation, which is linked to alpha-tubulin-based cell restructuring and control of cell cycle progression, were identified as a major complex trait for early de novo programming (‘CoV-MAC-TED’) during SARS-CoV-2 infection. This trait was highlighted as a critical target for developing early anti-viral/anti-SARS-CoV-2 strategies. To obtain this result, analyses had been performed on transcriptome data from diverse experimental cell systems. A call was released for wide data collection of the defined set of genes for transcriptome analyses, named ‘ReprogVirus’, which should be based on strictly standardized protocols and data entry from diverse virus types and variants into the ‘ReprogVirus Platform’. This platform is currently under development. However, so far, an in vitro cell system from primary target cells for virus attacks that could ideally serve for standardizing the data collection of early SARS-CoV-2 infection responses has not been defined. Results: Here, we demonstrate transcriptome-level profiles of the most critical ‘ReprogVirus’ gene sets for identifying ‘CoV-MAC-TED’ in cultured human nasal epithelial cells infected by two SARS-CoV-2 variants differing in disease severity. Our results (a) validate ‘Cov-MAC-TED’ as a crucial trait for early SARS-CoV-2 reprogramming for the tested virus variants and (b) demonstrate its relevance in cultured human nasal epithelial cells. Conclusion: In vitro-cultured human nasal epithelial cells proved to be appropriate for standardized transcriptome data collection in the ‘ReprogVirus Platform’. Thus, this cell system is highly promising to advance integrative data analyses with the help of artificial intelligence methodologies for designing anti-SARS-CoV-2 strategies. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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13 pages, 2159 KiB

Open AccessArticle

Use of Stability Modeling to Support Accelerated Vaccine Development and Supply

by Cristiana Campa, Thierry Pronce, Marilena Paludi, Jos Weusten, Laura Conway, James Savery, Christine Richards and Didier Clénet

Vaccines 2021, 9(10), 1114; https://doi.org/10.3390/vaccines9101114 - 30 Sep 2021

Cited by 8 | Viewed by 4902

Abstract

Stability assessment of pharmaceuticals in specific storage and shipment conditions is a key requirement to ensure that safe and efficacious products are administered to patients. This is particularly relevant for vaccines, with numerous vaccines strictly requiring cold storage to remain stable. When stability [...] Read more.

Stability assessment of pharmaceuticals in specific storage and shipment conditions is a key requirement to ensure that safe and efficacious products are administered to patients. This is particularly relevant for vaccines, with numerous vaccines strictly requiring cold storage to remain stable. When stability evaluation is exclusively based on real-time data, it may represent a bottleneck for rapid and effective vaccine access. Stability modeling for vaccines represents a key resource to predict stability based on accelerated stability studies; nevertheless, this approach is not fully exploited for these kinds of products. This is likely because of the complexity and diversity of vaccines, as well as the limited availability of dedicated guidelines or illustrative case studies. This article reports a cross-company perspective on stability modeling for vaccines. Several examples, based on the direct experience of the contributors, demonstrate that modeling approaches can be highly valuable to predict vaccines’ shelf life and behavior during shipment or manipulation. It is demonstrated that modeling methodologies need to be tailored to the nature of the vaccine, the available prior knowledge, and the monitored attributes. Considering that the well-established strategies reported in ICH or WHO guidelines are not always broadly applicable to vaccines, this article represents an important source of information for vaccine researchers and manufacturers, setting the grounds for further discussion within the vaccine industry and with regulators. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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21 pages, 3773 KiB

Open AccessArticle

New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects

by Musa A. Said, Daoud J. O. Khan, Fawzia F. Al-blewi, Nadia S. Al-Kaff, Adeeb A. Ali, Nadjet Rezki, Mohamed Reda Aouad and Mohamed Hagar

Vaccines 2021, 9(9), 1012; https://doi.org/10.3390/vaccines9091012 - 11 Sep 2021

Cited by 25 | Viewed by 2883

Abstract

Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, ¹H NMR, ¹³C NMR, and CHN analysis). The spectral data analysis revealed that the [...] Read more.

Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, ¹H NMR, ¹³C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of trans-E and cis-E diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the trans-trans form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH–C=O group. The energy differences between the trans-trans on one side and syn-syn and syn-trans isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor N3 and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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15 pages, 3934 KiB

Open AccessFeature PaperArticle

Development of an mRNA-LNP Vaccine against SARS-CoV-2: Evaluation of Immune Response in Mouse and Rhesus Macaque

by Alireza Naderi Sohi, Jafar Kiani, Ehsan Arefian, Arezou Khosrojerdi, Zahra Fekrirad, Shokoofeh Ghaemi, Mohammad Kazem Zim, Arsalan Jalili, Nazila Bostanshirin and Masoud Soleimani

Vaccines 2021, 9(9), 1007; https://doi.org/10.3390/vaccines9091007 - 10 Sep 2021

Cited by 14 | Viewed by 14032

Abstract

Among the vaccines have been developed thus far against SARS-CoV-2, the mRNA-based ones have demonstrated more promising results regarding both safety and efficacy. Two remarkable features of the mRNA vaccines introduced by the Pfizer/BioNTech and Moderna companies are the use of (N¹ [...] Read more.

Among the vaccines have been developed thus far against SARS-CoV-2, the mRNA-based ones have demonstrated more promising results regarding both safety and efficacy. Two remarkable features of the mRNA vaccines introduced by the Pfizer/BioNTech and Moderna companies are the use of (N¹-methyl-pseudouridine-) modified mRNA and the microfluidics-based production of lipid nanoparticles (LNPs) as the carrier. In the present study, except Anti-Reverse Cap Analog (ARCA), no other nucleoside analogs were employed to synthesize Spike-encoding mRNA using the in vitro transcription (IVT) method. Furthermore, LNPs were prepared via the ethanol injection method commonly used for liposome formation as an alternative for microfluidics-based approaches. The produced mRNA-LNP vaccine was evaluated for nanoparticles characteristics, encapsulation and transfection efficiencies, in vitro cytotoxicity as well as stability and storability. The safety of vaccine was assessed in Balb/c mice injected with mRNA-LNPs containing 10 µg of spike-encoding mRNA. Eventually, the vaccine efficacy in inducing an immune response against SARS-CoV-2 was studied in Balb/c and C57BL/6 mice (received either 1 or 10 µg of mRNA) as well as in rhesus macaque monkeys (infused with mRNA-LNPs containing 100 µg of mRNA). The ELISA and virus neutralizing test (VNT) results showed a significant augmentation in the level of neutralizing antibodies against SARS-CoV-2. Moreover, the ELISA assay showed virus-specific IFN-γ secretion in immunized mice as a marker of T_H1 cell-based immune response, whereas favorably no change in the production of IL-4 was detected. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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12 pages, 906 KiB

Open AccessArticle

Early Serological Response to BNT162b2 mRNA Vaccine in Healthcare Workers

by Giovanna Cocomazzi, Valeria Piazzolla, Maria Maddalena Squillante, Stefano Antinucci, Vincenzo Giambra, Francesco Giuliani, Alberto Maiorana, Nicola Serra and Alessandra Mangia

Vaccines 2021, 9(8), 913; https://doi.org/10.3390/vaccines9080913 - 16 Aug 2021

Cited by 12 | Viewed by 2981

Abstract

Purpose: Clinical significance and durability of serological response after mRNA COVID-19 vaccines is under investigation. Data on early virological response are limited. To iden-tify potential predictors of antibody durability, circulating antibody levels were longitudinally ex-plored in healthcare workers included in a follow-up program [...] Read more.

Purpose: Clinical significance and durability of serological response after mRNA COVID-19 vaccines is under investigation. Data on early virological response are limited. To iden-tify potential predictors of antibody durability, circulating antibody levels were longitudinally ex-plored in healthcare workers included in a follow-up program for SARS-CoV-2 infection. Meth-ods: Subjects meeting the inclusion criteria signed an informed consent. Serum samples were col-lected at baseline, before the first BNT162b2 vaccine, at days 7, 21, 31, 90, and 180 days after the first dose. Serological evaluation was performed by QuantiVac Euroimmune anti-S1 antibody as-say. Only subjects followed-up until day 90 are here considered. Results: Of 340 taken into consid-eration, 265 subjects were naive, and 75 COVID-19 experienced. The former showed a progres-sive increase in their antibody levels before day 90 decline, while the latter showed antibody levels reaching a plateau at day 7 and slightly declining at day 90. All showed antibody levels higher than the assay cut-off at day 31 and 90. Among naive, 108 had an early response whose predic-tors were younger age and female gender (OR 0.94, 95% CI 0.91–0.96, p < 0.0001; and OR 2.58, 95% CI 1.48–4.51, p = 0.0009). Naive subjects experienced a day 30/90 decline in antibody levels, whereas experienced did not. Early response was an independent predictor of higher day 30/90 antibody levels decline (OR = 2.05, 95% CI 1.04–4.02; p = 0.037). Conclusions: Our results suggest that in healthcare workers early response might be inversely associated with antibody levels 90 days after BNT162b2 vaccine. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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8 pages, 4895 KiB

Open AccessArticle

Production of SARS-CoV-2 Virus-Like Particles in Insect Cells

by Youjun Mi, Tao Xie, Bingdong Zhu, Jiying Tan, Xuefeng Li, Yanping Luo, Fei Li, Hongxia Niu, Jiangyuan Han, Wei Lv and Juan Wang

Vaccines 2021, 9(6), 554; https://doi.org/10.3390/vaccines9060554 - 26 May 2021

Cited by 23 | Viewed by 4730

Abstract

Coronavirus disease (COVID-19) causes a serious threat to human health. Virus-like particles (VLPs) constitute a promising platform in SARS-CoV-2 vaccine development. In this study, the E, M, and S genes were cloned into multiple cloning sites of a new triple expression plasmid with [...] Read more.

Coronavirus disease (COVID-19) causes a serious threat to human health. Virus-like particles (VLPs) constitute a promising platform in SARS-CoV-2 vaccine development. In this study, the E, M, and S genes were cloned into multiple cloning sites of a new triple expression plasmid with one p10 promoter, two pPH promoters, and three multiple cloning sites. The plasmid was transformed into DH10 Bac^TMEscherichia coli competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9^TM insect cells to generate recombinant baculovirus. After ExpiSf9^TM cells infection with the recombinant baculovirus, the E, M, and S proteins were expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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19 pages, 2146 KiB

Open AccessArticle

Rotavirus as an Expression Platform of Domains of the SARS-CoV-2 Spike Protein

by Asha Ann Philip and John Thomas Patton

Vaccines 2021, 9(5), 449; https://doi.org/10.3390/vaccines9050449 - 03 May 2021

Cited by 19 | Viewed by 6165

Abstract

Among vaccines administered to children are those targeting rotavirus, a segmented double-stranded RNA virus that represents a major cause of severe gastroenteritis. To explore the feasibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that [...] Read more.

Among vaccines administered to children are those targeting rotavirus, a segmented double-stranded RNA virus that represents a major cause of severe gastroenteritis. To explore the feasibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding cassettes for NSP3, a translational 2A stop-restart signal, and a FLAG-tagged portion of the SARS-CoV-2 spike (S) protein: S1 fragment, N-terminal domain (NTD), receptor-binding domain (RBD), extended RBD (ExRBD), or S2 core (CR) domain. Generation of rSA11 containing the S1 coding sequence required a sequence insertion of 2.2 kbp, the largest such insertion yet introduced into the rotavirus genome. Immunoblotting showed that rSA11 viruses containing the smaller NTD, RBD, ExRBD, and CR coding sequences expressed S-protein products of expected size, with ExRBD expressed at highest levels. These rSA11 viruses were genetically stable during serial passage. In contrast, the rSA11 virus containing the full-length S coding sequence (rSA11/NSP3-fS1) failed to express its expected 80 kDa fS1 product, for unexplained reasons. Moreover, rSA11/NSP3-fS1 was genetically unstable, with variants lacking the S1 insertion appearing during serial passage. Nonetheless, these results emphasize the potential usefulness of rotavirus vaccines as expression vectors of immunogenic portions of the SARS-CoV-2 S protein, including NTD, RBD, ExRBD, and CR, that have sizes smaller than the S1 fragment. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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14 pages, 2789 KiB

Open AccessArticle

Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials

by Luigino Calzetta, Beatrice Ludovica Ritondo, Angelo Coppola, Maria Gabriella Matera, Nicola Di Daniele and Paola Rogliani

Vaccines 2021, 9(4), 341; https://doi.org/10.3390/vaccines9040341 - 01 Apr 2021

Cited by 23 | Viewed by 8539

Abstract

To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there [...] Read more.

To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there are modifying factors that may potentially influence the clinical efficacy of COVID-19 vaccines. A quantitative synthesis of data from Phase III trials was performed via pairwise and network meta-analyses, along with meta-regression analysis. Data from Phase III trials are currently available only for AZD1222, BNT162b2, mRNA-1237, and Sputnik V. Vaccination resulted to be generally effective (90.0%, 95%CI 72.6–96.4; p < 0.001), although the efficacy of AZD1222 (62.1%) introduced a significant level of heterogeneity in the meta-analysis (I² 92.17%, p < 0.001). No significant modifying factors resulted from the meta-regression analysis. However, considering the mRNA-based vaccines, a trend toward significance (p = 0.081) resulted for age. The network meta-analysis provided the following rank of effectiveness: BNT162b2 ≃ mRNA-1273 > Sputnik V >> AZD1222. In conclusion, no modifying factors seem to modulate the efficacy of vaccines against COVID-19. This quantitative synthesis will need to be updated as soon as further clinical results on the efficacy profile are available from Phase III trials for further licensed COVID-19 vaccines. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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19 pages, 6016 KiB

Open AccessArticle

Simultaneous CD8⁺ T-Cell Immune Response against SARS-Cov-2 S, M, and N Induced by Endogenously Engineered Extracellular Vesicles in Both Spleen and Lungs

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

Vaccines 2021, 9(3), 240; https://doi.org/10.3390/vaccines9030240 - 10 Mar 2021

Cited by 17 | Viewed by 3155

Abstract

Most advanced vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 are designed to induce antibodies against spike (S) protein. Differently, we developed an original strategy to induce CD8⁺ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). [...] Read more.

Most advanced vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 are designed to induce antibodies against spike (S) protein. Differently, we developed an original strategy to induce CD8⁺ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). This is a new vaccination approach based on intramuscular injection of DNA expression vectors coding for a biologically inactive HIV-1 Nef protein (Nef^mut) with an unusually high efficiency of incorporation into EVs, even when foreign polypeptides are fused to its C-terminus. Nanovesicles containing Nef^mut-fused antigens released by muscle cells can freely circulate into the body and are internalized by antigen-presenting cells. Therefore, EV-associated antigens can be cross-presented to prime antigen-specific CD8⁺ T-cells. To apply this technology to a strategy of anti-SARS-CoV-2 vaccine, we designed DNA vectors expressing the products of fusion between Nef^mut and different viral antigens, namely N- and C-terminal moieties of S (referred to as S1 and S2), M, and N. We provided evidence that all fusion products are efficiently uploaded in EVs. When the respective DNA vectors were injected in mice, a strong antigen-specific CD8⁺ T cell immunity became detectable in spleens and, most important, in lung airways. Co-injection of DNA vectors expressing the diverse SARS-CoV-2 antigens resulted in additive immune responses in both spleen and lungs. Hence, DNA vectors expressing Nef^mut-based fusion proteins can be proposed for new anti-SARS-CoV-2 vaccine strategies. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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Review

Jump to: Research, Other

38 pages, 1627 KiB

Open AccessReview

The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview

by Bruna Aparecida Souza Machado, Katharine Valéria Saraiva Hodel, Larissa Moraes dos Santos Fonseca, Luís Alberto Brêda Mascarenhas, Leone Peter Correia da Silva Andrade, Vinícius Pinto Costa Rocha, Milena Botelho Pereira Soares, Peter Berglund, Malcolm S. Duthie, Steven G. Reed and Roberto Badaró

Vaccines 2021, 9(11), 1345; https://doi.org/10.3390/vaccines9111345 - 17 Nov 2021

Cited by 23 | Viewed by 9683

Abstract

In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has [...] Read more.

In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has several advantages to vaccine development compared to other platforms, such as lower coast, the absence of cell cultures, and the possibility to combine different targets. During the COVID-19 pandemic, the use of mRNA as a vaccine became more relevant; two out of the four most widely applied vaccines against COVID-19 in the world are based on this platform. However, even though it presents advantages for vaccine application, mRNA technology faces several pivotal challenges to improve mRNA stability, delivery, and the potential to generate the related protein needed to induce a humoral- and T-cell-mediated immune response. The application of mRNA to vaccine development emerged as a powerful tool to fight against cancer and non-infectious and infectious diseases, for example, and represents a relevant research field for future decades. Based on these advantages, this review emphasizes mRNA and self-amplifying RNA (saRNA) for vaccine development, mainly to fight against COVID-19, together with the challenges related to this approach. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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23 pages, 2159 KiB

Open AccessReview

RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement

by Hana M. Abdelzaher, Asmaa S. Gabr, Basma M. Saleh, Rana M. Abdel Gawad, Ahmed A. Nour and Anwar Abdelanser

Vaccines 2021, 9(11), 1211; https://doi.org/10.3390/vaccines9111211 - 20 Oct 2021

Cited by 6 | Viewed by 5483

Abstract

mRNA vaccines have amassed a strong interest from scientists and nonscientists alike for their potential in treating cancer and curbing the spread of infectious diseases. Their success has been bolstered by the COVID-19 pandemic as mRNA vaccines for the SARS-CoV-2 virus showed unrivaled [...] Read more.

mRNA vaccines have amassed a strong interest from scientists and nonscientists alike for their potential in treating cancer and curbing the spread of infectious diseases. Their success has been bolstered by the COVID-19 pandemic as mRNA vaccines for the SARS-CoV-2 virus showed unrivaled efficiency and success. The strategy relies on the delivery of an RNA transcript that carries the sequence of an antigenic molecule into the body’s cells where the antigen is manufactured. The lack of use of infectious pathogens and the fact that they are made of nucleic acids render these vaccines a favorable alternative to other vaccination modalities. However, mRNA vaccination still suffers from a great deal of hurdles starting from their safety, cellular delivery, uptake and response to their manufacturing, logistics and storage. In this review, we examine the premise of RNA vaccination starting from their conceptualization to their clinical applications. We also thoroughly discuss the advances in the field of RNA vaccination for infectious diseases. Finally, we discuss the challenges impeding their progress and shed light on potential areas of research in the field. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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24 pages, 1127 KiB

Open AccessReview

COVID-19 Animal Models and Vaccines: Current Landscape and Future Prospects

by Shen Wang, Ling Li, Feihu Yan, Yuwei Gao, Songtao Yang and Xianzhu Xia

Vaccines 2021, 9(10), 1082; https://doi.org/10.3390/vaccines9101082 - 26 Sep 2021

Cited by 8 | Viewed by 7878

Abstract

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is [...] Read more.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates, and other susceptible animals have been involved in the study of COVID-19. Moreover, 117 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines, and messenger ribonucleic acid (mRNA) vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models for COVID-19 vaccine evaluation and advanced vaccines with an efficacy range from about 50% to more than 95%. In addition, we point out future directions for COVID-19 animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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18 pages, 1711 KiB

Open AccessReview

SARS-CoV-2 Neutralizing Antibodies: A Network Meta-Analysis across Vaccines

by Paola Rogliani, Alfredo Chetta, Mario Cazzola and Luigino Calzetta

Vaccines 2021, 9(3), 227; https://doi.org/10.3390/vaccines9030227 - 05 Mar 2021

Cited by 46 | Viewed by 27148

Abstract

Background: There are no studies providing head-to-head comparison across SARS-CoV-2 vaccines. Therefore, we compared the efficacy of candidate vaccines in inducing neutralizing antibodies against SARS-CoV-2. Methods: A network meta-analysis was performed to compare the peak levels of SARS-CoV-2 neutralizing antibodies across [...] Read more.

Background: There are no studies providing head-to-head comparison across SARS-CoV-2 vaccines. Therefore, we compared the efficacy of candidate vaccines in inducing neutralizing antibodies against SARS-CoV-2. Methods: A network meta-analysis was performed to compare the peak levels of SARS-CoV-2 neutralizing antibodies across candidate vaccines. Data were reported as standardized mean difference (SMD) since the outcome was assessed via different metrics and methods across the studies. Results: Data obtained from 836 healthy adult vaccine recipients were extracted from 11 studies. BBIBP-CorV, AZD1222, BNT162b2, New Crown COVID-19, and Sputnik V induced a very large effect on the level of neutralizing antibodies (SMD > 1.3); CoVLP, CoronaVac, NVX-CoV2373, and Ad5-nCoV induced a large effect (SMD > 0.8 to ≤1.3); and Ad26.COV2.S induced a medium effect (SMD > 0.5 to ≤0.8). BBIBP-CorV and AZD122 were more effective (p < 0.05) than Ad26.COV2.S, Ad5–nCoV, mRNA-1237, CoronaVac, NVX–CoV2373, CoVLP, and New Crown COVID-19; New Crown COVID-19 was more effective (p < 0.05) than Ad26.COV2.S, Ad5–nCoV, and mRNA-1237; CoronaVac was more effective (p < 0.05) than Ad26.COV2.S and Ad5–nCoV; and Sputnik V and BNT162b2 were more effective (p < 0.05) than Ad26.COV2.S. In recipients aged ≤60 years, AZD1222, BBIBP-CorV, and mRNA-1237 were the most effective candidate vaccines. Conclusion: All the candidate vaccines induced significant levels of SARS-CoV-2 neutralizing antibodies, but only AZD1222 and mRNA-1237 were certainly tested in patients aged ≥70 years. Compared with AZD1222, BNT162b and mRNA-1237 have the advantage that they can be quickly re-engineered to mimic new mutations of SARS-CoV-2. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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Other

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7 pages, 237 KiB

Open AccessCommentary

A Commentary on Realities of Developing COVID-19 Vaccines Discussed through the Global Health Safety Perspective

by Wedad Saeed Al-Qahtani and Fatmah Ahmed Safhi

Vaccines 2021, 9(3), 274; https://doi.org/10.3390/vaccines9030274 - 18 Mar 2021

Cited by 5 | Viewed by 12611

Abstract

SARS-CoV-2 (or simply COVID-19) remains to be a global pandemic issue affecting millions, thus urging the world’s scientific community to develop efficient vaccine and design adequate measures of disease control. Currently, the most economically viable solution to infections and viruses is vaccination, despite [...] Read more.

SARS-CoV-2 (or simply COVID-19) remains to be a global pandemic issue affecting millions, thus urging the world’s scientific community to develop efficient vaccine and design adequate measures of disease control. Currently, the most economically viable solution to infections and viruses is vaccination, despite the possible concerns about side effects from implementing quickly developed vaccine. The current commentary intends to explain the health and safety related to COVID-19 vaccines via a prism of global health safety. Scientists across the globe, along with companies from both public and private sectors, have predictably arranged cooperative programs to learn about COVID-19, along with taking simultaneous steps on devising vaccine and preparing effective treatments plans. Presently, several clinical trials to approve the efficiency of proposed vaccine solutions have been made successfully. Global health safety concerns on vaccine’s efficiency such as high costs of production, provision of vaccine to developing countries, and its influence on the global economy are addressed. This commentary reflects on current efforts related to the development of vaccine against COVID-19, which currently affects the global health status and economy. In addition, the commentary aims at addressing potential risks related to the development of COVID-19 vaccine from the global health safety perspective. Full article

(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)

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