Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 14, 2024

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants approved COVID-19 vaccines necessitates vaccines. We evaluated two doses, 28 days apart, ARCT-154, a self-amplifying mRNA vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety reactogenicity outcomes were unsolicited adverse events (AE) after each dose, solicited local systemic AE 7 serious AEs throughout the study. immunogenicity outcome was immune response as neutralizing antibodies second dose. Efficacy assessed primary secondary 3b. ARCT-154 well tolerated generally mild-moderate transient AEs. Four weeks dose 94.1% (95% CI: 92.1-95.8) vaccinees seroconverted for antibodies, geometric mean-fold rise from baseline 14.5 13.6-15.5). Of 640 cases confirmed eligible efficacy analysis most due to Delta (B.1.617.2) variant. 56.6% 48.7- 63.3) any COVID-19, 95.3% (80.5-98.9) severe COVID-19. vaccination is tolerated, immunogenic efficacious, particularly disease.

Language: Английский

---

Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 13, 2023

Abstract Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form virus mRNA26 based Pfizer/BNT162b2 are widely distributed. Beyond ability to induce production neutralizing antibodies, they might lead generation antibodies attenuating disease by recruiting cytotoxic opsonophagocytic functions. However, Fc-effector functions vaccine induced much less studied than neutralization. Here, using systems serology, we follow longitudinal profiles CoronaVac BNT162b2 up until five months following two-dose regimen. Compared BNT162b2, responses wane more slowly, albeit levels remain lower that recipients throughout entire observation period. mRNA boosting responses, including response Omicron variant, significantly higher peak antibody functional increased humoral breadth. In summary, show platform-induced not limited neutralization but rather utilise dependent effector We demonstrate this functionality wanes different kinetics can be rescued expanded via subsequent homologous heterologous vaccination.

Language: Английский

---

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: April 27, 2023

Abstract Background The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. influence of multiple factors on vaccine effectiveness (VE) during long-term use against variants is not well understood. Methods We selected published or preprinted articles from PubMed, Embase, Scopus, Web Science, medRxiv, BioRxiv, WHO database by 31 August 2022. included observational studies that assessed VE completed primary series homologous booster infection severe COVID-19. DerSimonian Laird random-effects models calculate pooled estimates conducted meta-regression with an information theoretic approach based Akaike’s Information Criterion select model identify associated VE. Results Fifty-one eligible 151 were included. For prevention infection, study region, variants, time since vaccination; was significantly decreased Omicron compared Alpha ( P = 0.021), 52.8% (95% CI, 43.3 60.7%) Delta 16.4% 9.5 22.8%) Omicron, dose 65.2% 48.3 76.6%) 20.3% 10.5 28.0%) Omicron; after 180 days 0.022). COVID-19, doses, age, design, population type; increased 0.001) primary; though Gamma 0.034), 0.001), Alpha, VEs all above 60% each variant. Conclusions Inactivated protection moderate, 6 months following vaccination, restored vaccination. greatest boosting did decrease over time, sustained for series, more evidence needed assess duration varied most notably Omicron. It necessary ensure vaccination everyone vaccines continue monitoring virus evolution Trial registration PROSPERO, CRD42022353272.

Language: Английский

---

Real-life effectiveness of COVID-19 vaccine during the Omicron variant-dominant pandemic: how many booster doses do we need?

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(1)

Published: Jan. 30, 2023

The surge in coronavirus disease 2019 (COVID-19) caused by the Omicron variants of severe acute respiratory syndrome 2 necessitates researches to inform vaccine effectiveness (VE) and other preventive measures halt pandemic. A test-negative case-control study was conducted among adults (age ≥18 years) who were at-risk for COVID-19 presented nasopharyngeal real-time polymerase chain reaction testing during variant-dominant period Thailand (1 January 2022-15 June 2022). All participants prospectively followed up development 14 days after enrolment. Vaccine estimated adjusted characteristics associated with COVID-19. Of 7971 included individuals, there 3104 cases 4867 controls. VE persons receiving 2-dose, 3-dose, 4-dose regimens preventing infection moderate-to-critical diseases 33%, 48%, 62% 60%, 74%, 76%, respectively. generally higher those last dose within 90 compared more than prior highest observed individuals regimen, CoronaVac-CoronaVac-ChAdOx1 nCoV-19-BNT162b2 both (65%) (82%). Our demonstrated increased along an increase number doses received. Current vaccination programmes should focus on reducing severity mandate at least one booster dose. heterologous boosters viral vector mRNA vaccines highly effective can be used previously received primary series inactivated vaccine.

Language: Английский

---

Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 30, 2023

Abstract Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based easier and cheaper produce do not require special storage/transportation conditions, they suitable for low-/middle-income countries. Here, we report our development studies with receptor binding domain of Delta Plus strain (RBD-DP) which caused increased hospitalizations compared other variants. First, expressed RBD-DP in Pichia pastoris yeast system upscaled it a 5-L fermenter production. After three-step purification, obtained > 95% purity from protein yield 1 g/L supernatant. Several biophysical biochemical characterizations were performed confirm its identity, stability, functionality. Then, was formulated different contents Alum CpG mice immunization. three doses immunization, IgG titers sera reached 10 6 most importantly showed high T-cell responses required an effective prevent severe COVID-19 disease. A live neutralization test both Wuhan (B.1.1.7) (B.1.617.2) antibody content strains. challenge study infected K18-hACE2 transgenic good immunoprotective activity no viruses lungs lung inflammation all immunized mice.

Language: Английский

---

Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 omicron infection and related hospital admission among people with substance use disorder in Hong Kong: a matched case-control study

The Lancet Psychiatry, Journal Year: 2023, Volume and Issue: 10(6), P. 403 - 413

Published: May 1, 2023

Language: Английский

---

From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 459 - 459

Published: April 25, 2024

Understanding the antibody response to SARS-CoV-2, virus responsible for COVID-19, is crucial comprehending disease progression and significance of vaccine therapeutic development. The emergence highly contagious variants poses a significant challenge humoral immunity, underscoring necessity grasping intricacies specific antibodies. This review emphasizes pivotal role antibodies in shaping immune responses their implications diagnosing, preventing, treating SARS-CoV-2 infection. It delves into kinetics characteristics explores current antibody-based diagnostics, discussing strengths, clinical utility, limitations. Furthermore, we underscore potential SARS-CoV-2-specific antibodies, various therapies such as monoclonal polyclonal anti-cytokines, convalescent plasma, hyperimmunoglobulin-based therapies. Moreover, offer insights vaccines, emphasizing neutralizing order confer immunity along with emerging concern (VOCs) circulating Omicron subvariants. We also highlight challenges field, risks antibody-dependent enhancement (ADE) shed light on associated original antigenic sin (OAS) effect long COVID. Overall, this intends provide valuable insights, which are advancing sensitive diagnostic tools, identifying efficient therapeutics, developing effective vaccines combat evolving threat global scale.

Language: Английский

---

Effectiveness and coverage of COVID-19 vaccination among the infection-naive population: A community-based retrospective cohort study in China

Vaccine, Journal Year: 2025, Volume and Issue: 50, P. 126836 - 126836

Published: Feb. 10, 2025

Language: Английский

---

Neurobiological Alterations Induced by SARS-CoV-2: Insights from Variant-Specific Host Gene Expression Patterns in hACE2-Expressing Mice

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 329 - 329

Published: Feb. 27, 2025

Since the onset of COVID-19 pandemic, various severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have emerged. Although primary site SARS-CoV-2 infection is lungs, it can also affect brain and induce neurological symptoms. However, specific effects different on remain unclear. In this study, a whole-transcriptome analysis was conducted using tissues K18-hACE2 mice infected with ancestral B.1 (Wuhan) variant major concern, including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) B.1.529 (Omicron). After sequencing, differential gene expression, ontology (GO) genome pathway enrichment analyses were performed. An Immune Cell Abundance Identifier (ImmuCellAI) used to identify abundance cell populations. Additionally, RT-qPCR validate RNA-seq data. The viral load hierarchical clustering divided samples into two clusters notable differences in expression at day 6 post-infection for all compared control group. GO Kyoto Encyclopedia genes genomes revealed similar patterns variants. ImmuCellAI changes immune populations, decrease CD4+ T B proportions increase CD8+ dendritic proportions. A co-expression network that some genes, such as STAT1, interleukin-6 (IL-6) tumor necrosis factor alpha (TNF-α), dysregulated IL-6, CXCL10 IRF7 further validated analysis. conclusion, study provides, first time, an extensive transcriptome mouse after

Language: Английский

---

Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian hamsters

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(1), P. e1011805 - e1011805

Published: Jan. 10, 2024

Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters evaluate hybrid induction. The mRNA vaccine, BNT162b2, was dosed induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of or variants concern (VoCs). Vaccination reduced morbidity and controlled lung for Alpha allowed Beta, Delta Mu-challenged hamsters. primed T cell responses that were boosted by infection. Infection back-boosted neutralizing VoCs. resulted more cross-reactive sera, reflected smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status disease course suggests a role interstitial macrophages vaccine-mediated protection. Therefore, vaccination, even the absence high antibodies serum, correlates with recall broadly reactive B- T-cell responses.

Language: Английский

---