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Keywords = XBB.1.5 vaccines

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26 pages, 6162 KiB  
Article
Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
by Fani Pantouli, Vanessa Silva-Moraes and Ted M. Ross
Vaccines 2025, 13(6), 607; https://doi.org/10.3390/vaccines13060607 - 4 Jun 2025
Abstract
Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, [...] Read more.
Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses. Full article
(This article belongs to the Special Issue 3rd Edition: Safety and Autoimmune Response to SARS-CoV-2 Vaccination)
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19 pages, 665 KiB  
Article
Real-World Effectiveness of Boosting Against Omicron Hospitalization in Older Adults, Stratified by Frailty
by Liang En Wee, Enoch Xue Heng Loy, Jue Tao Lim, Wei Hao Kwok, Calvin Chiew, Christopher Lien, Barbara Helen Rosario, Ian Yi Onn Leong, Reshma Aziz Merchant, David Chien Boon Lye and Kelvin Bryan Tan
Vaccines 2025, 13(6), 565; https://doi.org/10.3390/vaccines13060565 - 26 May 2025
Viewed by 287
Abstract
Background/Objectives: Older adults with frailty are at-risk of worse outcomes following respiratory-viral-infections such as COVID-19. Data on effectiveness of vaccination/boosting in frail older adults during Omicron is lacking. Methods: National healthcare-claims data and COVID-19 registries were utilized to enroll a cohort of older [...] Read more.
Background/Objectives: Older adults with frailty are at-risk of worse outcomes following respiratory-viral-infections such as COVID-19. Data on effectiveness of vaccination/boosting in frail older adults during Omicron is lacking. Methods: National healthcare-claims data and COVID-19 registries were utilized to enroll a cohort of older Singaporeans (≥60 years) as of 1 January 2022, divided into low/intermediate/high-risk for frailty; matching weights were utilized to adjust for sociodemographic differences/vaccination uptake at enrolment across frailty categories. Competing-risk-regression (Fine-Gray) taking death as a competing risk, with matching weights applied, was utilized to compare risks of COVID-19-related hospitalizations and severe COVID-19 across frailty levels (low/intermediate/high-risk), with estimates stratified by booster status. Individuals were followed up until study end-date (20 December 2023). Results: 874,160 older adults were included during Omicron-predominant transmission; ~10% had intermediate/high-frailty-risk. Risk of hospitalization/severe COVID-19 was elevated in those with intermediate/high-frailty-risk up to XBB/JN.1 transmission. Boosting was associated with decreased risk of COVID-19-related hospitalization across all frailty categories in infection-naïve individuals. However, in infection-naïve older adults with high-frailty-risk, while receipt of first boosters was associated with lower risk of COVID-19-hospitalization/severe COVID-19, additional booster doses did not reduce risk. In reinfected older adults, first boosters were still associated with lower hospitalization risk (adjusted-hazards-ratio, aHR = 0.55, 95% CI = 0.33–0.92) among the non-frail, but not in the intermediate/high-frailty-risk minority. Conclusions: First boosters were associated with reduced adverse COVID-19 outcomes across all frailty categories in infection-naïve older adults during Omicron. However, in the high-frailty minority, boosting did not additionally reduce risk in reinfected individuals with hybrid immunity, and beyond the first booster for infection-naïve individuals. Full article
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16 pages, 2352 KiB  
Article
XBB.1.5 RBD-Based Bivalent Vaccines Induced Antibody Responses Against SARS-CoV-2 Variants in Mice
by Jiawen Liu, Tiantian Wang, Hongying Ren, Ruixi Liu, Qian Wang, Jun Wu and Bo Liu
Vaccines 2025, 13(5), 543; https://doi.org/10.3390/vaccines13050543 - 20 May 2025
Viewed by 348
Abstract
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In [...] Read more.
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB.1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN.1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered Pichia pastoris was utilized to produce a recombinant XBB.1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB.1.5 RBD was mixed with Al(OH)3:CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB.1.5 RBD was mixed with the Beta (B.1.351), Delta (B.1.617.2), or Omicron (BA.2) RBDs (1:1 ratio), along with Al(OH)3:CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA.2, XBB.1.5, and JN.1 compared to those in mice immunized solely with Al(OH)3:CpG, as demonstrated by pseudovirus virus assays. The XBB.1.5/Delta RBD and XBB.1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA.2, XBB.1.5, JN.1, and KP.2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB.1.5 RBD-based and XBB.1.5/Delta RBD-based vaccines could neutralize the authentic XBB.1.16 virus. (5) Conclusions: The XBB.1.5/Beta and XBB.1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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19 pages, 827 KiB  
Review
Omicron Variant Could Be an Antigenic Shift of SARS-CoV-2
by Anju Kaushal
COVID 2025, 5(5), 73; https://doi.org/10.3390/covid5050073 - 14 May 2025
Viewed by 417
Abstract
In the past 5 years, the COVID-19 pandemic has experienced frequently changing variants contextualizing immune evasion. The emergence of Omicron with >30–50 mutations on the spike gene has shown a sharp divergence from its relative VOCs, such as WT, Alpha, Beta, Gamma, and [...] Read more.
In the past 5 years, the COVID-19 pandemic has experienced frequently changing variants contextualizing immune evasion. The emergence of Omicron with >30–50 mutations on the spike gene has shown a sharp divergence from its relative VOCs, such as WT, Alpha, Beta, Gamma, and Delta. The requisition of prime boosting was essential within 3–6 months to improve the Nab response that had been not lasted for longer. Omicron subvariant BA.1.1 was less transmissible, but with an extra nine mutations in next variant BA.2 made it more transmissible. This remarkable heterogeneity was reported in ORF1ab or TRS sites, ORF7a, and 10 regions in the genomic sequences of Omicron BA.2 and its evolving subvariants BA.4.6, BF.7, BQ.2, BF. 7, BA.2.75.2, and BA.5 (BQ.1 and BQ.1.1). The mutational stability of subvariants XBB, XBB 1, XBB 1.5, and XBB 1.6 conferred a similar affinity towards ACE-2. This phenomenon has been reported in breakthrough infections and after booster vaccinations producing hybrid immunity. The reduced pathogenic nature of Omicron has implicated its adaptation either through immunocompromised individuals or other animal hosts. The binding capacity of RBD and ACE-2, including the proteolytic priming via TMPRSS2, reveals its (in-vitro) transmissibility behavior. RBD mutations signify transmissibility, S1/S2 enhances virulence, while S2 infers the effective immunogenic response. Initial mutations D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H, and G496S were found to increase the Ab escape. Some mutations such as, R346K, L452R, and F486Vwere seen delivering immune pressure. HR2 region (S2) displayed mutations R436S, K444T, F486S, and D1199N with altered spike positions. Later on, the booster dose or breakthrough infections contributed to elevating the immune profile. Several other mutations in BA.1.1-N460K, R346T, K444T, and BA.2.75.2-F486S have also conferred the neutralization resistance. The least studied T-cell response in SARS-CoV-2 affects HLA- TCR interactions, thus, it plays a role in limiting the virus clearance. Antigenic cartographic analysis has also shown Omicron’s drift from its predecessor variants. The rapidly evolving SARS-CoV-2 variants and subvariants have driven the population-based immunity escape in fully immunized individuals within short period. This could be an indication that Omicron is heading towards endemicity and may evolve in future with subvariants could lead to outbreaks, which requires regular surveillance. Full article
(This article belongs to the Section Human or Animal Coronaviruses)
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16 pages, 3274 KiB  
Article
Long-Term Dynamics of SARS-CoV-2 Variant-Specific Neutralizing Antibodies Following mRNA Vaccination and Infection
by Veronika Vaňová, Jana Náhliková, Martina Ličková, Monika Sláviková, Ivana Kajanová, Ľubomíra Lukáčiková, Miroslav Sabo, Žofia Rádiková, Silvia Pastoreková and Boris Klempa
Viruses 2025, 17(5), 675; https://doi.org/10.3390/v17050675 - 6 May 2025
Viewed by 431
Abstract
Understanding the long-term dynamics of SARS-CoV-2 neutralizing antibodies is critical for evaluating vaccine-induced protection and informing booster strategies. In this longitudinal study, we analyzed 114 serum samples from 19 individuals across six time points over a three-year period following mRNA vaccination (Comirnaty) and [...] Read more.
Understanding the long-term dynamics of SARS-CoV-2 neutralizing antibodies is critical for evaluating vaccine-induced protection and informing booster strategies. In this longitudinal study, we analyzed 114 serum samples from 19 individuals across six time points over a three-year period following mRNA vaccination (Comirnaty) and natural SARS-CoV-2 infection. Using pseudotype-based neutralization assays against nine SARS-CoV-2 variants, including major Omicron subvariants (BA.1–BA.5, BQ.1.1, XBB), and anti-S1 IgG ELISA, we observed that antibody levels peaked after the third vaccine dose and remained relatively stable two years later. Neutralization titers rose markedly after the second and third doses, with the highest neutralization observed at two years post-booster. Strong correlations were found between anti-S1 IgG levels and mean neutralization titers for pre-Omicron variants (r = 0.79–0.93; p < 0.05), but only moderate for Omicron subvariants (r ≈ 0.50–0.64). Notably, hybrid immunity (vaccination plus infection) resulted in higher neutralization titers at the final time point compared to vaccine-only participants. The lowest neutralization was observed against XBB, underscoring the immune evasiveness of emerging variants. These findings support the importance of booster vaccination and highlight the added durability of hybrid immunity in long-term protection. Full article
(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 3rd Edition)
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10 pages, 2546 KiB  
Brief Report
Humoral and Cell-Mediated Immunity Against SARS-CoV-2 in Healthcare Personnel Who Received Multiple mRNA Vaccines: A 4-Year Observational Study
by Hideaki Kato, Kaori Sano, Kei Miyakawa, Takayuki Kurosawa, Kazuo Horikawa, Yayoi Kimura, Atsushi Goto and Akihide Ryo
Infect. Dis. Rep. 2025, 17(3), 42; https://doi.org/10.3390/idr17030042 - 29 Apr 2025
Viewed by 344
Abstract
Background/Objectives: The long-term effects of multiple updated vaccinations against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have not been clarified. Humoral or cellular immunity dynamics in healthcare workers for four years were analyzed. Methods: Blood samples were collected at five time points from April [...] Read more.
Background/Objectives: The long-term effects of multiple updated vaccinations against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have not been clarified. Humoral or cellular immunity dynamics in healthcare workers for four years were analyzed. Methods: Blood samples were collected at five time points from April 2021 to January 2024. Humoral immunity was analyzed using the 50% neutralizing titer (NT50) against the original Omicron XBB and Omicron BA.2.86 strains and cellular immunity were analyzed using the ELISpot interferon-gamma releasing assay. NT50s and the spot-forming count (SFC) of the ELISpot assay were compared in the SARS-CoV-2 Omicron XBB-, Omicron-infected, and uninfected subjects. Results: 32 healthcare workers (median age, 47 years) who received 3–7 vaccine doses were enrolled. The NT50s against the original strain decreased after the second vaccination but were maintained after the third vaccine dose. NT50s against the Omicron XBB and BA.2.86 strains were detected before the Omicron vaccine was introduced and increased following the updated vaccination. The NT50s against the Omicron XBB and BA.2.86 strains were elevated after natural infection by the Omicron strain, albeit without differences compared with the findings in uninfected subjects. Multivariate regression analysis revealed no confounder that affected the antibody titer against the BA.2.86 strain at the fifth blood sampling. The median number of SFCs ranged from 78 to 208 after the first two doses. Conclusions: Multiple vaccinations induced the production of antibodies with divergent activity against emerging mutant strains and enhanced protective effects against the original strain. This finding supported the importance of updated vaccination. Full article
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50 pages, 3587 KiB  
Review
Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern
by Ankita Saha, Sounak Ghosh Roy, Richa Dwivedi, Prajna Tripathi, Kamal Kumar, Shashank Manohar Nambiar and Rajiv Pathak
Vaccines 2025, 13(4), 424; https://doi.org/10.3390/vaccines13040424 - 17 Apr 2025
Viewed by 1473
Abstract
Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as [...] Read more.
Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford–AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)
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10 pages, 654 KiB  
Communication
Immune Response Against Recent Omicron Sub-Lineages in Persons with HIV Receiving a Protein-Based or mRNA XBB.1.5 SARS-CoV-2 Booster Vaccine
by Alessandra Vergori, Giulia Matusali, Eleonora Cimini, Alessandro Cozzi Lepri, Valentina Mazzotta, Davide Mariotti, Francesca Colavita, Simona Gili, Flavia Cristofanelli, Marisa Fusto, Roberta Gagliardini, Jessica Paulicelli, Federico Cecilia, Enrico Girardi, Fabrizio Maggi and Andrea Antinori
Int. J. Mol. Sci. 2025, 26(8), 3521; https://doi.org/10.3390/ijms26083521 - 9 Apr 2025
Viewed by 430
Abstract
The new Nuvaxovid protein-based and Pfizer-BioNTech mRNA-based vaccines targeting Omicron XBB.1.5 were available during the 2023–2024 autumn/winter vaccination campaign for frail individuals, including people with HIV (PWH). We assessed the immune response in 51 PWH on stable ART who received a booster with [...] Read more.
The new Nuvaxovid protein-based and Pfizer-BioNTech mRNA-based vaccines targeting Omicron XBB.1.5 were available during the 2023–2024 autumn/winter vaccination campaign for frail individuals, including people with HIV (PWH). We assessed the immune response in 51 PWH on stable ART who received a booster with either the Nuvaxovid protein-based (n = 25) or Pfizer-BioNTech mRNA-based XBB.1.5 vaccine (n = 26). The median age was 57 years (IQR 51–65), the median count of CD4 at T0 was 652/mmc (503–935), and CD4 nadir was 226/mmc (95–340). Samples were collected before (T0) and one month after (T1) the booster. We measured neutralizing antibodies (nAbs) titers against D614G, XBB.1.6, and JN.1 variants and T-cell IFN-γ levels produced upon specific stimulation. Regardless of the vaccine used, we observed a marked increase in nAbs titers from T0 to T1 against all the subvariants, but no evidence for a change in IFN-γ release. After controlling for confounders, there was no evidence for a difference in the T0-T1 change in nAbs titers against XBB.1.16 and JN.1 by the type of vaccine, while Nuvaxovid determined a smaller increase in D614G nAbs (p = 0.008). The XBB.1.5 protein-based vaccine’s immunogenicity as a fifth or later booster was comparable to the Pfizer-BioNTech mRNA vaccine, particularly against recent Omicron variants. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 387 KiB  
Article
Estimating the Public Health and Economic Impact of Annual mRNA COVID-19 Vaccination for Adults Aged 50 and Older in South Korea’s Endemic Era
by Jaehee Jung, Dain Lee, Hee-Do Yang, Ah-Young Kim, Haeun Lee, Minkyoung Kang, Ekkehard Beck, Keya Joshi, Youngju Kang and Hye-Young Kang
Vaccines 2025, 13(4), 386; https://doi.org/10.3390/vaccines13040386 - 3 Apr 2025
Viewed by 1038
Abstract
Background/Objectives: COVID-19 continues to challenge public health due to emerging variants. To mitigate this, the Korea Disease Control and Prevention Agency (KDCA) recommends annual COVID-19 vaccination, but uptake remains suboptimal. This study evaluates the public health and economic impact of annual mRNA COVID-19 [...] Read more.
Background/Objectives: COVID-19 continues to challenge public health due to emerging variants. To mitigate this, the Korea Disease Control and Prevention Agency (KDCA) recommends annual COVID-19 vaccination, but uptake remains suboptimal. This study evaluates the public health and economic impact of annual mRNA COVID-19 vaccination for adults aged 50 and older in South Korea during the 2024–2025 season, focusing on hospitalizations and costs. Methods: We estimated hospitalizations prevented by the mRNA-1273 XBB.1.5 containing vaccine by calculating symptomatic infection incidence rates, hospitalization rates among unvaccinated individuals, vaccine effectiveness (VE) against hospitalization, and vaccination rates. Incidence rates among the unvaccinated with an annual vaccine were derived by adjusting overall infection rates based on vaccination coverage and VE against COVID-19 hospitalization rates. Hospitalization costs were obtained from a real-world dataset, integrating the KDCA’s COVID-19 confirmed cases with National Health Insurance claims data. Comparative analyses between mRNA-1273 and BNT162b2 used published meta-analysis results. Results: Assuming vaccination rates remain consistent with the 2023–2024 season, mRNA-1273 is projected to prevent 37,200 hospitalizations and save USD 77.2 million in healthcare costs during the 2024–2025 season compared to no annual vaccination. Compared to BNT162b2, it is expected to prevent an additional 13,260 hospitalizations saving USD 27.5 million. If vaccination rates increased to match influenza, hospitalizations prevented by mRNA-1273 could rise to 79,800 with USD 164.2 million in healthcare savings compared to no annual vaccination. Conclusion: Annual mRNA COVID-19 vaccination with mRNA-1273 substantially reduces hospitalizations and healthcare costs. Increasing vaccination rates are essential to maximize public health benefits. Full article
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16 pages, 2258 KiB  
Article
Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV
by Xiaoqing Guan, Abhishek K. Verma, Qian Liu, Melissa Palacios, Abby E. Odle, Stanley Perlman and Lanying Du
Vaccines 2025, 13(3), 293; https://doi.org/10.3390/vaccines13030293 - 10 Mar 2025
Viewed by 824
Abstract
Background. The pathogenic coronaviruses (CoVs) MERS-CoV and SARS-CoV-2, which are responsible for the MERS outbreak and the COVID-19 pandemic, respectively, continue to infect humans, with significant adverse outcomes. There is a continuing need to develop mucosal vaccines against these respiratory viral pathogens to [...] Read more.
Background. The pathogenic coronaviruses (CoVs) MERS-CoV and SARS-CoV-2, which are responsible for the MERS outbreak and the COVID-19 pandemic, respectively, continue to infect humans, with significant adverse outcomes. There is a continuing need to develop mucosal vaccines against these respiratory viral pathogens to prevent entry and replication at mucosal sites. The receptor-binding domain (RBD) of the CoV spike (S) protein is a critical vaccine target, and glycan masking is a unique approach for designing subunit vaccines with improved neutralizing activity. Methods. We evaluated the efficacy of mucosal immunity, broad neutralizing activity, and cross-protection afforded by a combined glycosylated mucosal subunit vaccine encoding the RBDs of the original SARS-CoV-2 strain (SARS2-WT-RBD), the Omicron-XBB.1.5 variant (SARS2-Omi-RBD), and MERS-CoV (MERS-RBD). Results. Intranasal administration of the three-RBD protein cocktail induced effective, durable IgA and systemic IgG antibodies specific for the S protein of these CoVs, thereby neutralizing infection by pseudotyped SARS-CoV-2-WT, Omicron-XBB.1.5, and MERS-CoV. The mucosal vaccine cocktail protected immunized mice from challenge with SARS-CoV-2 Omicron-XBB.1.5 and MERS-CoV, leading to a significant reduction in the viral titers in the lungs. By contrast, the individual glycosylated RBD proteins only induced such immune responses and neutralizing antibodies against either SARS-CoV-2 or MERS-CoV, protecting against subsequent challenge with either SARS-CoV-2 or MERS-CoV; they did not provide simultaneous protection against both CoVs. Conclusions. This study describes a unique strategy for designing efficacious mucosal subunit vaccines that induce durable mucosal immunity, cross-neutralizing activity, and cross-protection against SARS-CoV-2 and MERS-CoV, highlighting the potential for the design of mucosal vaccines against other pathogens. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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15 pages, 5066 KiB  
Article
A Hidden Guardian: The Stability and Spectrum of Antibody-Dependent Cell-Mediated Cytotoxicity in COVID-19 Response in Chinese Adults
by Jinge Cao, Mengze Gan, Zhihao Zhang, Xiaosong Lin, Qi Ouyang, Hui Fu, Xinyue Xu, Zhen Wang, Xinlian Li, Yaxin Wang, Hao Cai, Qing Lei, Li Liu, Hao Wang and Xionglin Fan
Vaccines 2025, 13(3), 262; https://doi.org/10.3390/vaccines13030262 - 28 Feb 2025
Viewed by 704
Abstract
Objectives: Identifying immune-protective biomarkers is crucial for the effective management and mitigation of current and future COVID-19 outbreaks, particularly in preventing or counteracting the immune evasion exhibited by the Omicron variants. The emergence of SARS-CoV-2 variants, especially those within the Omicron lineage, has [...] Read more.
Objectives: Identifying immune-protective biomarkers is crucial for the effective management and mitigation of current and future COVID-19 outbreaks, particularly in preventing or counteracting the immune evasion exhibited by the Omicron variants. The emergence of SARS-CoV-2 variants, especially those within the Omicron lineage, has highlighted their capacity to evade neutralizing antibodies, emphasizing the need to understand the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in combating these infections. Methods: This study, conducted in Qichun City, Hubei province, from December 2021 to March 2023, involved 50 healthy Chinese adults who had received two doses of inactivated vaccines and had subsequently experienced mild infections with the Omicron BA.5 variant. Blood samples from these 50 healthy Chinese adults were collected at six distinct time points: at baseline and at the 1st, 3rd, 6th, and 9th months following the third dose of the inactivated vaccine, as well as 3 months post-breakthrough infection. Their sera were analyzed to assess ADCC and neutralization effects. Results: The results indicated that the antibodies elicited by the inactivated SARS-CoV-2 vaccine targeted the spike protein, exhibiting both pre-existing neutralizing and ADCC activities against Omicron variants BA.5 and XBB.1.5. Notably, the ADCC activity demonstrated greater stability compared to that of the neutralizing effects, persisting for at least 15 months post-vaccination, and could be augmented by additional vaccine doses and breakthrough infections. The ADCC effect associated with hybrid immunity effectively targets a spectrum of prospective Omicron variants, including BA.2.86, CH.1.1, EG.5.1, and JN.1. Conclusions: In light of its stability and broad-spectrum efficacy, we recommend the use of the ADCC effect as a biomarker for assessing protective immunity and guiding the development of vaccines and monoclonal antibodies. Full article
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10 pages, 687 KiB  
Brief Report
XBB1.5-Adapted COVID-19 Vaccine Acceptance Among Dialysis and Kidney Transplant Patients: A Bi-National Survey Study
by Georg Beilhack, Rossella Monteforte, Florian Frommlet, Alicia Faltum, Timna Agur and Ruth Rahamimov
Vaccines 2025, 13(3), 213; https://doi.org/10.3390/vaccines13030213 - 21 Feb 2025
Viewed by 577
Abstract
Background: A decrease in governmental vaccination initiatives and diminishing public enthusiasm for vaccines could jeopardize vaccine uptake, potentially endangering those who are most at risk. In this survey study, we evaluated the current acceptance rates of the newly developed monovalent XBB1.5-adapted COVID-19 [...] Read more.
Background: A decrease in governmental vaccination initiatives and diminishing public enthusiasm for vaccines could jeopardize vaccine uptake, potentially endangering those who are most at risk. In this survey study, we evaluated the current acceptance rates of the newly developed monovalent XBB1.5-adapted COVID-19 vaccine among kidney transplant recipients and dialysis patients in Austria and Israel and identified factors influencing vaccine acceptance. Methods: The survey involved a total of 656 patients aged 18 and older and was carried out from 20 November to 21 December 2023, at the Medical University of Vienna, Austria and the Rabin Medical Center in Petah Tikva, Israel. Logistic regression analysis was used to explore the relationships between vaccine acceptance and variables such as age, gender, country, past COVID-19 infection status and severity, renal replacement therapy, education level, and willingness to receive the annual flu vaccine. Results: The survey showed that 54% of patients in Austria and 63% in Israel expressed acceptance of the modified XBB1.5-adapted COVID-19 vaccine. The main hesitancy was due to concerns about potential side effects, with 44% in Austria and 53% in Israel expressing apprehension. A willingness to receive the influenza vaccine, older age in Austria, and kidney transplant status in Israel were key predictors of greater COVID-19 vaccine acceptance. Conclusions: This study showed that more than 50% of our kidney transplant recipients and dialysis patients were willing to receive the adapted COVID-19 vaccine. Yet, vaccine hesitancy remained a significant barrier even among these high-risk groups, despite the availability of an updated COVID-19 vaccine targeting the Omicron subvariant XBB1.5. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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16 pages, 3602 KiB  
Article
Two Years of SARS-CoV-2 Omicron Genomic Evolution in Brazil (2022–2024): Subvariant Tracking and Assessment of Regional Sequencing Efforts
by Ueric José Borges de Souza, Fernando Rosado Spilki, Amilcar Tanuri, Paulo Michel Roehe and Fabrício Souza Campos
Viruses 2025, 17(1), 64; https://doi.org/10.3390/v17010064 - 4 Jan 2025
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Abstract
SARS-CoV-2, the virus responsible for COVID-19, has undergone significant genetic evolution since its emergence in 2019. This study examines the genomic diversity of SARS-CoV-2 in Brazil after the worst phase of the pandemic, the wider adoption of routine vaccination, and the abolishment of [...] Read more.
SARS-CoV-2, the virus responsible for COVID-19, has undergone significant genetic evolution since its emergence in 2019. This study examines the genomic diversity of SARS-CoV-2 in Brazil after the worst phase of the pandemic, the wider adoption of routine vaccination, and the abolishment of other non-pharmacological preventive measures from July 2022 to July 2024 using 55,951 sequences retrieved from the GISAID database. The analysis focuses on the correlation between confirmed COVID-19 cases, sequencing efforts across Brazilian states, and the distribution and evolution of viral lineages. Our findings reveal significant regional disparities in genomic surveillance, with São Paulo and Rio de Janeiro recovering the largest number of genomes, while Tocantins and Amazonas showed higher sequencing rates relative to their reported case numbers, indicating proactive surveillance efforts. We identified 626 distinct SARS-CoV-2 lineages circulating in Brazil, with dominant subvariants shifting over time from BA.5 in 2022 to XBB and JN.1 in 2023–2024. The emergence of new subvariants in this new epidemiological scenario underscores the importance of ongoing genomic surveillance to track viral evolution and inform public health strategies, providing valuable information to update vaccines and implement other measures, such as lockdowns, mask usage, social distancing, health education, and self-testing. Full article
(This article belongs to the Section Coronaviruses)
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17 pages, 3950 KiB  
Article
T Cell Responses to BA.2.86 and JN.1 SARS-CoV-2 Variants in Elderly Subjects
by Irene Segato, Dalila Mele, Greta Forlani, Daniela Dalla Gasperina, Mario U. Mondelli and Stefania Varchetta
Vaccines 2024, 12(12), 1451; https://doi.org/10.3390/vaccines12121451 - 23 Dec 2024
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Abstract
Background/Objectives: New SARS-CoV-2 variants are continuously emerging, making it essential to assess the efficacy of vaccine-induced immune protection. Limited information is available regarding T cell responses to BA.2.86 and JN.1 variants, particularly in elderly individuals. Methods: We evaluated T cell and total IgG [...] Read more.
Background/Objectives: New SARS-CoV-2 variants are continuously emerging, making it essential to assess the efficacy of vaccine-induced immune protection. Limited information is available regarding T cell responses to BA.2.86 and JN.1 variants, particularly in elderly individuals. Methods: We evaluated T cell and total IgG responses against the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 strain, as well as BA.2.86 and JN.1 omicron subvariants, in two groups of subjects. One group consisted of SARS-CoV-2-exposed elderly individuals who were fully vaccinated with the BNT162B2 mRNA vaccine, with a booster dose of the updated 2023–2024 COVID-19 vaccine (XBB.1.5) at least 15 days after receiving a booster dose of the updated 2023–2024 COVID-19 vaccine. The second group consisted of healthcare workers who were unexposed to SARS-CoV-2 one month after the booster dose of the first-generation BNT162b2 mRNA vaccine. T cell activation-induced markers (AIM) and IFN-γ secretion were evaluated by flow cytometry and ELISpot assays, respectively. Results: Elderly subjects showed reduced IgG levels against JN.1 compared with the ancestral strain. BA.2.86 stimulation resulted in lower IFN-γ levels in the elderly versus the COVID-19-naïve group. AIM analysis showed that among T cells, CD4+ were the most responsive, with a reduced proportion of JN.1-reactive CD4+ T cells compared with the ancestral strain in the SARS-CoV-2-unexposed group. Despite receiving the updated booster, the elderly group showed reduced CD4+ T cell reactivity to BA.2.86. Conclusions: The XBB.1.5-containing vaccine induced lower CD4+ T cell responses against BA.2.86 in the elderly. CD4+ T cells from BNT16b2-vaccinated, COVID-19-naïve subjects recognized ancestral and BA.2.86 RBD strains while showing reduced responses to JN.1. These results emphasize the need for tailored vaccine strategies for emerging variants, particularly in vulnerable populations. Full article
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11 pages, 4549 KiB  
Article
Immune Response to SARS-CoV-2 XBB.1.5 and JN.1 Variants Following XBB.1.5 Booster Vaccination in Liver Transplant Recipients
by Philippa von der Schulenburg, Georg M. N. Behrens, Markus Hoffmann, Alexandra Linke, Inga Nehlmeier, Amy Madeleine Kempf, Metodi Stankov, Marc Lütgehetmann, Jacqueline Jahnke-Triankowski, Marylyn M. Addo, Lutz Fischer, Ansgar W. Lohse, Stefan Pöhlmann, Julian Schulze zur Wiesch and Martina Sterneck
Viruses 2024, 16(12), 1942; https://doi.org/10.3390/v16121942 - 19 Dec 2024
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Abstract
Background/Objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.1. Methods: This study evaluated humoral and cellular immune responses in 34 liver transplant [...] Read more.
Background/Objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.1. Methods: This study evaluated humoral and cellular immune responses in 34 liver transplant recipients (LTRs) with varying SARS-CoV-2 immune histories before and after receiving a BNT162b2 Omicron XBB.1.5 booster vaccination. The assessment involved variant-specific serology, pseudovirus neutralization tests, and Interferon-γ release assays. Results: Participants had a median of four prior vaccinations, with 91.2% having a history of infection. Post-vaccination, significant increases in both Wuhan anti-S and Omicron-specific IgG antibodies and improved neutralization of B.1, XBB.1.5, and JN.1 pseudovirus particles were observed. Also, T-cell responses significantly increased post-vaccination. However, 17.6% of LTRs had no neutralizing antibodies against XBB.1.5 and JN.1, while 100% of healthy controls did. Shortly after vaccination, 18% of patients developed mild COVID-19. These LTRs had particularly low immune responses at baseline. Conclusions: The monovalent XBB.1.5 booster improved overall SARS-CoV-2-specific immunity. However, some LTRs still showed low or undetectable immune responses, indicating that ongoing monitoring and further booster doses are necessary in this high-risk group. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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