Vaccines

Research

25 pages, 4161 KiB

Open AccessArticle

Systemic and Mucosal Antibody Responses to SARS-CoV-2 Variant-Specific Prime-and-Boost and Prime-and-Spike Vaccination: A Comparison of Intramuscular and Intranasal Bivalent Vaccine Administration in a Murine Model

by Mariam Maltseva, Yannick Galipeau, Pauline McCluskie, Nicolas Castonguay, Curtis L. Cooper and Marc-André Langlois

Vaccines 2025, 13(4), 351; https://doi.org/10.3390/vaccines13040351 - 25 Mar 2025

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Abstract

Background: The rapid genetic evolution of SARS-CoV-2 has led to the emergence of immune-evading, highly transmissible variants of concern (VOCs). This prompts the need for next-generation vaccines that elicit robust mucosal immunity in the airways to directly curb viral infection. Objective: Here, we [...] Read more.

Background: The rapid genetic evolution of SARS-CoV-2 has led to the emergence of immune-evading, highly transmissible variants of concern (VOCs). This prompts the need for next-generation vaccines that elicit robust mucosal immunity in the airways to directly curb viral infection. Objective: Here, we investigate the impact of heterologous variant prime–boost regimens on humoral responses, focusing on intramuscular (IM) and intranasal (IN) routes of administration. Using a murine model, we assessed the immunogenicity of unadjuvanted protein boosts with Wu-1, Omicron BA.4/5, or Wu-1 + BA.4/5 spike antigens following monovalent or bivalent IM priming with mRNA-LNP vaccines. Results: IM priming induced strong systemic total and neutralizing antibody responses that were further enhanced by IN boosts with BA.4/5. IN boosting achieved the broadest serum neutralization across all VOCs tested. Notably, bivalent mRNA-LNP IM priming induced robust, cross-variant serum neutralizing antibody production, independent of subsequent IN boost combinations. Conclusions: Our findings highlight the benefit of including distinct antigenic variants in the prime vaccination followed by a variant-tailored IN boost to elicit both systemic and mucosal variant-specific responses that are potentially capable of reducing SARS-CoV-2 transmission. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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16 pages, 6378 KiB

Open AccessArticle

Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve

by Enes Karaman, Adem Yavuz, Erol Karakas, Esra Balcioglu, Busra Karaca, Hande Nur Doganay, Koray Gorkem Sacinti and Orhan Yildiz

Vaccines 2025, 13(4), 345; https://doi.org/10.3390/vaccines13040345 - 24 Mar 2025

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Abstract

Objectives: This study aimed to elucidate the effects of messenger RNA (mRNA) and inactivated coronavirus disease 2019 (COVID-19) vaccines on ovarian histology and reserve in rats. Methods: Thirty female Wistar albino rats, aged 16–24 weeks, were randomly divided into three groups [...] Read more.

Objectives: This study aimed to elucidate the effects of messenger RNA (mRNA) and inactivated coronavirus disease 2019 (COVID-19) vaccines on ovarian histology and reserve in rats. Methods: Thirty female Wistar albino rats, aged 16–24 weeks, were randomly divided into three groups (n = 10): control, mRNA vaccine, and inactivated vaccine groups. Each vaccine group received two doses (on day 0 and day 28) at human-equivalent doses. Four weeks post-second vaccination, ovarian tissues were harvested for analysis. Results: Immunohistochemical analysis was performed to evaluate the expression of transforming growth factor beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), caspase-3, and anti-Müllerian hormone (AMH) in ovarian follicles. Both vaccines induced significant increases in TGF-β1, VEGF, and caspase-3 expression, with more pronounced effects in the mRNA vaccine group. Conversely, AMH expression in the granulosa cells of primary, secondary, and antral follicles showed marked reductions (p < 0.001). The counts of primordial, primary, and secondary follicles decreased significantly in the inactivated vaccine group relative to controls and further in the mRNA vaccine group compared to the inactivated group (p < 0.001). Additionally, the mRNA vaccine group exhibited a decrease in antral and preovulatory follicles and an increase in atretic follicles compared to the other groups (p < 0.05). The serum AMH level was diminished with the mRNA vaccination in comparison with the control and inactivated groups. Conclusions: Our findings suggest that both mRNA and inactivated COVID-19 vaccines may detrimentally impact ovarian reserve in rats, primarily through accelerated follicular loss and alterations in apoptotic pathways during folliculogenesis. Given these observations in a rat model, further investigations into the vaccines’ effects on human ovarian reserve are needed. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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9 pages, 202 KiB

Open AccessArticle

COVID-19 Vaccination and Acute Anterior Uveitis—A Case Control Study

by Asaf Shemer, Amit Toledano, Aya Altarescu, Biana Dubinsky-Pertzov, Assaf Rozenberg, Idan Hecht, Adi Einan-Lifshitz and Eran Pras

Vaccines 2025, 13(2), 176; https://doi.org/10.3390/vaccines13020176 - 12 Feb 2025

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Abstract

Objective: To evaluate the association between the BNT162b2 (Pfizer-BioNTech^®) coronavirus disease vaccine and new-onset anterior uveitis. Methods: A retrospective case control study of patients admitted and diagnosed with new-onset acute anterior uveitis, and matched controls admitted for other reasons (1:3 ratio), [...] Read more.

Objective: To evaluate the association between the BNT162b2 (Pfizer-BioNTech^®) coronavirus disease vaccine and new-onset anterior uveitis. Methods: A retrospective case control study of patients admitted and diagnosed with new-onset acute anterior uveitis, and matched controls admitted for other reasons (1:3 ratio), was completed. Rates of exposure to the BNT162b2 vaccine were compared between groups, and odds ratios for exposure to the vaccine were calculated. A secondary analysis of the overall number of patients with new-onset anterior uveitis in the six preceding years was conducted. This study was conducted in one academic center in Israel. Results: A total of 16 patients were admitted for acute anterior uveitis during the study period. Of the 16 cases, 11 (69%) received the first dose of the BNT162b2 vaccine prior to presentation and 8 (50%) also received the second dose. This compares to 39 (81.2%) in the control group. The odds ratio for exposure to the vaccine among cases was 0.508 (95% confidence interval 0.141–1.829, p = 0.300). Compared with preceding years, the rate of cases diagnosed with acute anterior uveitis in 2021 was similar to the six preceding years (mean 11.8 ± 3.4 cases). Conclusions: In this case control study and comparison with preceding years, we found no evidence to suggest an association between vaccination with the BNT162b2 (Pfizer-BioNTech^®) COVID-19 vaccine and new-onset acute anterior uveitis. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

12 pages, 1593 KiB

Open AccessArticle

Assessing Torquetenovirus (TTV) as a Biomarker for Immune Responses to SARS-CoV-2 mRNA Vaccines in People Living with HIV and Healthy Individuals

by Claudia Minosse, Pietro Giorgio Spezia, Valentina Mazzotta, Giulia Matusali, Silvia Meschi, Francesca Colavita, Davide Mariotti, Stefania Notari, Alessandra Vergori, Daniele Focosi, Enrico Girardi, Andrea Antinori and Fabrizio Maggi

Vaccines 2025, 13(2), 153; https://doi.org/10.3390/vaccines13020153 - 1 Feb 2025

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Background: Torquetenovirus (TTV) viremia is increasingly recognized as a marker of immune competence. In the context of COVID-19, TTV viral load (VL) has been shown to predict anti-Spike antibody levels in severely immunocompromised patients. This study aimed to evaluate whether pre-vaccine TTV [...] Read more.

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a marker of immune competence. In the context of COVID-19, TTV viral load (VL) has been shown to predict anti-Spike antibody levels in severely immunocompromised patients. This study aimed to evaluate whether pre-vaccine TTV VL could predict humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines in people living with HIV (PLWH) and healthy individuals (HP). Methods: TTV VL was measured via real-time PCR in serum samples collected before the second and third doses of mRNA vaccines in 93 PLWH and 48 HP (second dose) and 255 PLWH and 48 HP (third dose). Immune responses were assessed through anti-SARS-CoV-2 receptor-binding domain (RBD) IgG, neutralizing antibodies, and IFN-γ release. Statistical analyses included correlation studies between TTV VL and vaccine-induced immune responses. Results: TTV VL did not significantly correlate with anti-RBD IgG or neutralizing antibody levels in either cohort; highlighting its limited predictive value for humoral responses in relatively immunocompetent populations. However, a strong inverse correlation was observed between TTV VL and IFN-γ release after the third, but not the second, vaccine dose. These findings suggest that higher TTV VL, indicative of reduced immune competence, may impair T-cell-mediated immunity to vaccines. Conclusions: In virologically suppressed PLWH and HP, TTV VL is not a reliable predictor of humoral immune responses to COVID-19 vaccines. However, its inverse relationship with cellular responses warrants further investigation in more immunosuppressed populations. These results reinforce the continuum model of TTV VL as a biomarker, with predictive utility increasing alongside the degree of immunosuppression Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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14 pages, 1034 KiB

Open AccessArticle

Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data

by Tom C. Quach, Mitchell G. Miglis, Lu Tian, Hector Bonilla, Phillip C. Yang, Lauren Grossman, Amogha Paleru, Vincent Xin, Anushri Tiwari, Robert W. Shafer and Linda N. Geng

Vaccines 2024, 12(12), 1427; https://doi.org/10.3390/vaccines12121427 - 18 Dec 2024

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Abstract

Introduction: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 [...] Read more.

Introduction: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed. Methods: We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients (n = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC (n = 484). Findings: Within the PASC Clinic patient cohort (n = 128), 58.6% (n = 75) were female, and 41.4% (n = 53) were male; 50% (n = 64) were white, and 38.3% (n = 49) were non-white. A total of 60.2% (n = 77) of PASC Clinic patients reported no change in their PASC symptoms after vaccination, 17.2% (n = 22) reported improved symptoms, and 22.7% (n = 29) reported worsened symptoms. In the multinational survey cohort (n = 484), 380 were from the U.S., and 104 were from outside the U.S.; 88.4% (n = 428) were female, and 11.6% (n = 56) were male; and 88.8% (n = 430) were white, and 11.2% (n = 54) were non-white. The distribution of survey self-reported vaccine effects on PASC symptoms was 20.2% worsened (n = 98), 60.5% no effect (n = 293), and 19.2% improved (n = 93). In both cohorts, demographic features, including age, sex, and race/ethnicity, were not significantly associated with post-vaccination PASC symptom changes. There was also a non-significant difference in the median dates of COVID-19 infection among the different outcomes. BMI was significant for symptom improvement (p = 0.026) in the PASC Clinic cohort, while a history of booster doses was significant for symptom improvement (p < 0.001) in the survey cohort. Conclusions: Most individuals with PASC did not report significant changes in their overall PASC symptoms following COVID-19 vaccinations received after PASC onset. Further research is needed to better understand the relationship between COVID-19 vaccinations and PASC. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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13 pages, 1024 KiB

Open AccessArticle

Impact of Repeated Variant Exposures on Cellular and Humoral Immunogenicity Induced by SARS-CoV-2 Vaccines

by Leire Fernández-Ciriza, José Luis del Pozo, Nazaret Betanzos, Álvaro González, Alejandro Fernandez-Montero, Francisco Carmona-Torre, Marta Vidaurreta, Silvia Carlos and Gabriel Reina

Vaccines 2024, 12(12), 1408; https://doi.org/10.3390/vaccines12121408 - 13 Dec 2024

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Background/Objectives: The emergence of the Omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies have shown that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remain limited. This study aimed to assess Anti-S-RBD antibodies [...] Read more.

Background/Objectives: The emergence of the Omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies have shown that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remain limited. This study aimed to assess Anti-S-RBD antibodies and interferon-γ levels in healthcare workers 12 months after receiving bivalent Original/Omicron BA.4-5 fourth SARS-CoV-2 vaccine. Methods: In this prospective cohort study, 549 healthcare workers were categorized by the initial vaccination schedule, with 229 individuals having received the fourth SARS-CoV-2 vaccine dose. Blood samples were collected from all participants 12 months post-vaccination. Results: Significant differences in Anti-S-RBD antibody levels were observed between those receiving a fourth dose and those who did not, while no differences were seen in interferon-γ levels. After 12 months, there were no significant differences in humoral and cellular immunity response between volunteers primoinfected or reinfected across different periods by the Omicron variant. A multivariable analysis revealed an association between high antibody levels (>6000 U/mL) and interferon-γ levels (OR: 3.13; 95% CI: 1.3–7.7; p < 0.05). Regarding primary vaccine schedules, participants vaccinated with ChAdOx1 (a single or double dose) had notably lower antibody levels compared to those who received mRNA-based vaccines. Additionally, the study shows a higher frequency of multiple infections among those with a single-dose ChAdOx1 primary schedule (OR: 6.24; 95% CI: 1.25–31.15; p < 0.01). Conclusions: Overall, mRNA-based vaccines exhibited stronger long-term immunogenicity. Repeated exposure to the Omicron variant seems to mitigate immune imprinting from the wild-type SARS-CoV-2. An association was observed between high antibody levels and a strong cellular response, although the correlation was not linear. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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14 pages, 1260 KiB

Open AccessArticle

Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021–May 2023

by Camelia Savulescu, Albert Prats-Uribe, Kim Brolin, Zvjezdana Lovrić Makarić, Anneli Uusküla, Georgios Panagiotakopoulos, Colm Bergin, Catherine Fleming, Antonella Agodi, Paolo Bonfanti, Rita Murri, Viesturs Zvirbulis, Dace Zavadska, Konstanty Szuldrzynski, Ausenda Machado, Corneliu Petru Popescu, Mihai Craiu, Maria Cisneros, Miriam Latorre-Millán, Goranka Petrović, Liis Lohur, Kyriaki Tryfinopoulou, Jonathan McGrath, Lauren Ferguson, Martina Barchitta, Anna Spolti, Katleen de Gaetano Donati, Ilze Abolina, Dagne Gravele, Vânia Gaio, Simin Aysel Florescu, Mihaela Lazar, Pilar Subirats, Laura Clusa Cuesta, Gordan Sarajlić, Marina Amerali, Jacklyn Sui, Claire Kenny, Venerando Rapisarda, Marianna Rossi, Silvia Lamonica, Dainis Krievins, Elza Anna Barzdina, Ana Palmira Amaral, Alma Gabriela Kosa, Victor Daniel Miron, Carmen Muñoz-Almagro, Ana María Milagro, Sabrina Bacci, Piotr Kramarz, Anthony Nardone and the VEBIS HCW VE Study Group Show full author list Hide full author list

Vaccines 2024, 12(11), 1295; https://doi.org/10.3390/vaccines12111295 - 19 Nov 2024

Cited by 3 | Viewed by 3334

Abstract

Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 [...] Read more.

Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May–6 September 2021), Delta (7 September–14 December 2021), and Omicron (15 December 2021–2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: −25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7–90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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25 pages, 9144 KiB

Open AccessArticle

Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates

by Ekaterina Stepanova, Irina Isakova-Sivak, Victoria Matyushenko, Daria Mezhenskaya, Igor Kudryavtsev, Arina Kostromitina, Anna Chistiakova, Alexandra Rak, Ekaterina Bazhenova, Polina Prokopenko, Tatiana Kotomina, Svetlana Donina, Vlada Novitskaya, Konstantin Sivak, Dzhina Karal-Ogly and Larisa Rudenko

Vaccines 2024, 12(10), 1099; https://doi.org/10.3390/vaccines12101099 - 26 Sep 2024

Cited by 2 | Viewed by 4374

Abstract

Background. Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding [...] Read more.

Background. Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site. In this study, we present the results of preclinical evaluation of the developed bivalent vaccine in a non-human primate model. Methods. Rhesus macaques (Macaca mulatta) (n = 3 per group) were immunized intranasally with 7.5 lg EID₅₀ of the LAIV/CoV-2 bivalent vaccine, a control non-modified H3N2 LAIV or a placebo (chorioallantoic fluid) using a sprayer device, twice, with a 28-day interval. The blood samples were collected at days 0, 3, 28 and 35 for hematological and biochemical assessment. Safety was also assessed by monitoring body weight, body temperature and clinical signs of the disease. Immune responses to influenza virus were assessed both by determining serum antibody titers in hemagglutination inhibition assay, microneutralization assay and IgG ELISA. T-cell responses were measured both to influenza and SARS-CoV-2 antigens using ELISPOT and flow cytometry. Three weeks after the second immunization, animals were challenged with 10⁵ PFU of Delta SARS-CoV-2. The body temperature, weight and challenge virus shedding were monitored for 5 days post-challenge. In addition, virus titers in various organs and histopathology were evaluated on day 6 after SARS-CoV-2 infection. Results. There was no toxic effect of the immunizations on the hematological and coagulation hemostasis of animals. No difference in the dynamics of the average weight and thermometry results were found between the groups of animals. Both LAIV and LAIV/CoV-2 variants poorly replicated in the upper respiratory tract of rhesus macaques. Nevertheless, despite this low level of virus shedding, influenza-specific serum IgG responses were detected in the group of monkeys immunized with the LAIV/CoV-2 bivalent but not in the LAIV group. Furthermore, T-cell responses to both influenza and SARS-CoV-2 viruses were detected in the LAIV/CoV-2 vaccine group only. The animals were generally resistant to SARS-CoV-2 challenge, with minimal virus shedding in the placebo and LAIV groups. Histopathological changes in vaccinated animals were decreased compared to the PBS group, suggesting a protective effect of the chimeric vaccine candidate. Conclusions. The candidate bivalent vaccine was safe and immunogenic for non-human primates and warrants its further evaluation in clinical trials. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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17 pages, 4076 KiB

Open AccessArticle

Immunogenicity and Protective Efficacy of Baculovirus-Expressed SARS-CoV-2 Envelope Protein in Mice as a Universal Vaccine Candidate

by Tuba Çiğdem Oğuzoğlu, Alireza Hanifehnezhad, Saber Delpasand Khabbazi, İlke Karayel-Hacıoğlu, Onur Kaynarcalıdan, Zehra Fırat, Nazlıcan Filazi, Eda Erdem-Şahinkesen, Buket Gül, Muhammed Cesim Karabulut, Enes Koba, Ece Adıgüzel, Elif İrem Şenlik, Emrah Korkulu, Cansu Demirden, İlker Şahinkesen, Ahmet Ceylan, Hacer Muratoğlu, Sevil Vural, Zihni Demirbağ and Aykut Özkul Show full author list Hide full author list

Vaccines 2024, 12(9), 977; https://doi.org/10.3390/vaccines12090977 - 28 Aug 2024

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Abstract

The envelope (env) protein of SARS-CoV-2, a pivotal component of the viral architecture, plays a multifaceted role in viral assembly, replication, pathogenesis, and ion channel activity. These features make it a significant target for understanding virus–host interactions and developing vaccines to combat COVID-19. [...] Read more.

The envelope (env) protein of SARS-CoV-2, a pivotal component of the viral architecture, plays a multifaceted role in viral assembly, replication, pathogenesis, and ion channel activity. These features make it a significant target for understanding virus–host interactions and developing vaccines to combat COVID-19. Recent structural studies provide valuable insights into the conformational dynamics and membrane topology of the SARS-CoV-2 env protein, shedding light on its functional mechanisms. The strong homology and highly conserved structure of the SARS-CoV-2 env protein shape its immunogenicity and functional characteristics. This study examines the ability of the recombinant SARS-CoV-2 env protein to stimulate an immune response. In this study, recombinant envelope proteins were produced using the baculovirus expression system, and their potential efficacy was evaluated in both in vivo and in vitro models. Our results reveal that the env protein of SARS-CoV-2 stimulates humoral and cellular responses and highlight its potential as a promising vaccine candidate for combating the ongoing pandemic. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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13 pages, 2286 KiB

Open AccessArticle

Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates

by Urja Bhatt, Cecile Herate, Reynette Estelien, Francis Relouzat, Nathalie Dereuddre-Bosquet, Dawid Maciorowski, Cheikh Diop, Emma Couto, Jillian Staiti, Mariangela Cavarelli, Laëtitia Bossevot, Quentin Sconosciuti, Page Bouchard, Roger Le Grand, Luk H. Vandenberghe and Nerea Zabaleta

Vaccines 2024, 12(8), 882; https://doi.org/10.3390/vaccines12080882 - 2 Aug 2024

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Abstract

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, [...] Read more.

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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Review

Jump to: Research, Other

42 pages, 2428 KiB

Open AccessReview

SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development

by Fabrizio Angius, Silvia Puxeddu, Silvio Zaimi, Serena Canton, Sepehr Nematollahzadeh, Andrea Pibiri, Ilenia Delogu, Gualtiero Alvisi, Meng Ling Moi and Aldo Manzin

Vaccines 2025, 13(1), 17; https://doi.org/10.3390/vaccines13010017 - 28 Dec 2024

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The COVID-19 pandemic, driven by the rapid evolution of the SARS-CoV-2 virus, presents ongoing challenges to global public health. SARS-CoV-2 is characterized by rapidly evolving mutations, especially in (but not limited to) the spike protein, complicating predictions about its evolutionary trajectory. These mutations [...] Read more.

The COVID-19 pandemic, driven by the rapid evolution of the SARS-CoV-2 virus, presents ongoing challenges to global public health. SARS-CoV-2 is characterized by rapidly evolving mutations, especially in (but not limited to) the spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading to multiple pandemic waves with over half a billion cases and seven million deaths globally. Despite several strategies, from rapid vaccine development and administration to the design and availability of antivirals, including monoclonal antibodies, already having been employed, the persistent circulation of the virus and the emergence of new variants continue to result in high case numbers and fatalities. In the past four years, immense research efforts have contributed much to our understanding of the viral pathogenesis mechanism, the COVID-19 syndrome, and the host–microbe interactions, leading to the development of effective vaccines, diagnostic tools, and treatments. The focus of this review is to provide a comprehensive analysis of the functional impact of mutations on diagnosis, treatments, and vaccine effectiveness. We further discuss vaccine safety in pregnancy and the implications of hybrid immunity on long-term protection against infection, as well as the latest developments on a pan-coronavirus vaccine and nasal formulations, emphasizing the need for continued surveillance, research, and adaptive public health strategies in response to the ongoing SARS-CoV-2 evolution race. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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18 pages, 7626 KiB

Open AccessReview

Subsequent Waves of Convergent Evolution in SARS-CoV-2 Genes and Proteins

by Daniele Focosi, Pietro Giorgio Spezia and Fabrizio Maggi

Vaccines 2024, 12(8), 887; https://doi.org/10.3390/vaccines12080887 - 5 Aug 2024

Cited by 3 | Viewed by 2023

Abstract

Beginning in 2022, following widespread infection and vaccination among the global population, the SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines and past infections. This review covers the convergent evolution of structural, nonstructural, and accessory proteins in SARS-CoV-2, with a specific [...] Read more.

Beginning in 2022, following widespread infection and vaccination among the global population, the SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines and past infections. This review covers the convergent evolution of structural, nonstructural, and accessory proteins in SARS-CoV-2, with a specific look at common mutations found in long-lasting infections that hint at the virus potentially reverting to an enteric sarbecovirus type. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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Other

Jump to: Research, Review

12 pages, 1538 KiB

Open AccessBrief Report

STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease

by Simon Woelfel, Daniel Junker, Irina Bergamin, Pamela Meyer-Herbon, Roman Stillhard, Nicole Graf, Georg Leinenkugel, Joel Dütschler, Marius König, Livia Kammerlander, Rahel Häuptle, Sarah Zwyssig, Claudia Krieger, Samuel Truniger, Seraina Koller, Katline Metzger-Peter, Nicola Frei, STAR SIGN Study Investigators, Werner C. Albrich, Matthias Friedrich, Christine Bernsmeier, Jan Hendrik Niess, Wolfgang Korte, Justus J. Bürgi, Alex Dulovic, Nicole Schneiderhan-Marra, David Semela and Stephan Brand Show full author list Hide full author list

Vaccines 2024, 12(11), 1241; https://doi.org/10.3390/vaccines12111241 - 31 Oct 2024

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Abstract

Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first [...] Read more.

Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2–4 weeks following a fourth dose of XBB.1.5 mRNA vaccines. Results: Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05). Conclusion: XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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