zorecimeran (CV07050101) / CureVac - LARVOL DELTA

Advancing mRNA vaccines for infectious diseases: key components, innovations, and clinical progress. (PubMed, Essays Biochem) - "The clinical success of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) has fueled broader applications, including influenza, respiratory syncytial virus (RSV), Zika, and HIV. Notably, mRNA-1345 became the first FDA-approved RSV mRNA vaccine, while self-amplifying RNA and multivalent vaccines are advancing in trials. However, CureVac's CVnCoV failed due to lack of nucleoside modifications, and mRNA-1325 (Zika) showed poor immunogenicity. Additionally, mRNA-1365 (RSV) faced an FDA clinical hold due to safety concerns...Innovations such as lyophilization and selective organ targeting technology are being explored to improve stability extrahepatic delivery. This review examines mRNA vaccine optimization strategies, clinical progress, and challenges, providing insights into future developments in this evolving field."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Comparative efficacy of leading COVID-19 vaccines: A network meta-analysis. (PubMed, Indian J Med Res) - "The statistically significant direct estimates were obtained by Spikevax [VE: 93.29 (91.31, 95.27); P<0.05], Pfizer BioNTech [VE: 92.07 (90.03, 94.12); P<0.05], Sputnik [VE: 91.60 (85.60, 97.60); P<0.05], Novavax [VE: 88.99 (83.55, 94.42); P<0.05], Sinovac [VE: 83.50 (65.40, 101.60); P<0.05], Covifenz [VE: 77.27 (68.48, 86.06); P<0.05], Zifivax [VE: 75.94 (70.86, 81.02); P<0.05], Covishield [VE: 72.34 (67.12, 77.56); P<0.05], S-Trimer [VE: 71.61 (56.23, 86.98); P<0.05], Covaxin [VE: 70.81 (65.33, 76.29); P<0.05], Soberna [VE: 69.70 (56.50, 82.90); P<0.05], Zydus Cadila [VE: 66.60 (47.60, 85.60); P<0.05], CVnCoV [VE: 63.70 (52.20, 75.20); P<0.05], Convidecia [VE: 57.50 (39.70, 75.30); P <0.05], and Jcovden [VE : 52.42 (47.28, 57.57); P<0.05]. Spikevax emerged triumphant with an unparalleled P score of 0.95, solidifying its status as a top ranking prevention tool against the COVID-19 in our investigation. Our analysis reveals a..."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease

A phase 3, randomised, observer-blinded, placebo controlled-trial evaluating the safety and immunogenicity of investigational SARS-CoV-2 mRNA vaccine CVnCoV in adult healthcare workers in Mainz (Germany). (PubMed, Vaccine X) - P3 | "No safety concerns for CVnCoV were identified up to 1 year post second dose. IgG responses against SARS-CoV-2 were observed after two doses, with a higher seroconversion rate and antibody levels observed after second vaccination.Study registration: ClinicalTrials.gov NCT04674189, study period: 23rd of December 2020 to 8th of June 2022."

Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Phase 2b/3, Randomized, Observer-Blinded, Placebo-Controlled, Multicenter Clinical Study Evaluating the Efficacy and Safety of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults 18 Years of Age and Older (clinicaltrials.gov) - P2/3 | N=39680 | Completed | Sponsor: CureVac | Phase classification: P2b ➔ P2/3

Phase classification • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity. (PubMed, Vaccines (Basel)) - "Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CD4 • CD8 • CXCL11 • IFNA1 • IFNG • IL10

Comparative efficacy and safety of COVID-19 vaccines in phase III trials: a network meta-analysis. (PubMed, BMC Infect Dis) - "None of the different types of vaccines were significantly superior in terms of efficacy, while mRNA vaccines were significantly inferior in safety to other types. BNT162b2 had the highest efficacy in preventing symptomatic SARS-CoV-2 infection in adults and the elderly, whereas BIV1-CovIran had the lowest incidence of SAEs in adults."

Journal • P3 data • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A third dose of the unmodified COVID-19 mRNA vaccine CVnCoV enhances quality and quantity of immune responses. (PubMed, Mol Ther Methods Clin Dev) - "Administration of low dose mRNA led to fewer cells expressing antigen in vivo at the injection site and in the draining lymph nodes compared with a tenfold higher dose, possibly reducing the engagement of precursor cells with the antigen and resulting in the suboptimal response observed following two-dose vaccination schedules in phase IIb/III clinical trials of CVnCoV. However, when immune memory is established, a third dose efficiently boosts the immunological responses as well as improves antibody affinity and breadth."

Journal • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Optimised Non-Coding Regions of mRNA SARS-CoV-2 Vaccine CV2CoV Improves Homologous and Heterologous Neutralising Antibody Responses. (PubMed, Vaccines (Basel)) - "Significant cross-neutralisation of the SARS-CoV-2 variants, Alpha (B.1.1.7), Beta (B.1.351), and the 'mink' variant (B1.1.298) that were circulating at the time in early 2021 were also demonstrated. In addition, CV2CoV induced higher levels of antibodies at lower doses than CVnCoV, suggesting that dose-sparing could be possible with the next-generation SARS-CoV-2 vaccine, which could improve worldwide vaccine supply."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study. (PubMed, EClinicalMedicine) - "All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. No safety concerns arose. Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) "A way to make Europe"."

Journal • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain

Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: a phase 2 randomized study. (PubMed, Vaccine X) - "We confirmed that two 12 µg doses of CVnCoV had an acceptable safety profile, and induced robust immune responses. Marked humoral immune responses to homologous boosters suggest two doses had induced immune memory."

Journal • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4 • CD8

A Study to Evaluate the Safety and Immunogenicity of Vaccine CVnCoV in Healthy Adults in Germany for COVID-19 (clinicaltrials.gov) - P3 | N=2351 | Completed | Sponsor: CureVac AG | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Determine the Safety and Efficacy of SARS-CoV-2 mRNA Vaccine CVnCoV in Adults for COVID-19 (clinicaltrials.gov) - P2b | N=39693 | Completed | Sponsor: CureVac AG | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Blood Pressure Increase following COVID-19 Vaccination: A Systematic Overview and Meta-Analysis. (PubMed, J Cardiovasc Dev Dis) - "However, some questions regarding the safety of COVID-19 vaccines have been recently raised...Proportions of cases of stage III hypertension or hypertensive urgencies and emergencies was 0.6% (95% CI: 0.1% to 5.1%). In conclusion, abnormal BP is not rare after COVID-19 vaccination, but the basic mechanisms of this phenomenon are still unclear and require further research."

Journal • Retrospective data • Review • Hypertension • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis. (PubMed, BMC Med) - "Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta, Gamma, and Delta variants. Booster vaccination is more effective against Delta and Omicron variants. mRNA vaccines seem to have higher VE against Alpha, Beta, Gamma, and Delta variants over others."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVID-19: A Study to Evaluate Safety, Reactogenicity and Immunogenicity of the SARS-CoV-2 mRNA Vaccine CVnCoV in Adults With Co-morbidities (clinicaltrials.gov) - P3 | N=129 | Terminated | Sponsor: CureVac AG | Completed ➔ Terminated; The Principal Investigators and CureVac decided to terminate the trial early following a change to the risk/benefit profile.

Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Third Dose of the COVID-19 Vaccine, CVnCoV, Increased the Neutralizing Activity against the SARS-CoV-2 Wild-Type and Delta Variant. (PubMed, Vaccines (Basel)) - "Four weeks after the third dose on D180, the neutralizing titers for wild-type and Delta were two-fold higher in younger participants than in older participants; seroconversion rates were 100% for wild-type and Delta in the younger group and for Delta in the older group. A third CVnCoV dose induced similar levels of neutralizing responses against wild-type virus and the Delta variant in both naïve and pre-exposed participants, aligning with current knowledge from licensed COVID-19 vaccines that a third dose is beneficial against SARS-CoV-2 variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVID-19 Vaccines Safety Tracking (CoVaST) (clinicaltrials.gov) - P=N/A | N=30000 | Recruiting | Sponsor: Masaryk University | Trial completion date: Jan 2022 ➔ Dec 2026 | Trial primary completion date: Dec 2021 ➔ Dec 2025

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

A Dose-Confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults for COVID-19 (clinicaltrials.gov) - P2a | N=674 | Completed | Sponsor: CureVac AG | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Determine the Safety and Efficacy of SARS-CoV-2 mRNA Vaccine CVnCoV in Adults for COVID-19 (clinicaltrials.gov) - P2b | N=39693 | Active, not recruiting | Sponsor: CureVac AG | Trial primary completion date: Apr 2021 ➔ Jun 2022

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

OPTIMIZATION OF NONCODING REGIONS IMPROVES mRNA SARS-CoV-2 VACCINE IN NHPs (CROI 2022) - "The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans...Antibody responses correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of an mRNA SARS-CoV-2 vaccine in nonhuman primates."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Relating in vitro neutralisation level and protection in the CVnCoV (CUREVAC) trial. (PubMed, Clin Infect Dis) - "The vaccine candidate CVnCoV (CUREVAC) showed surprisingly low efficacy in a recent phase 3 trial compared with other mRNA vaccines. Here we show that the low efficacy follows from the dose used and the presence of SARS-CoV-2 variants, and is predicted by the neutralising antibody response induced by the vaccine."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults (clinicaltrials.gov) - P1; N=280; Completed; Sponsor: CureVac AG; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Most COVID-19 vaccines effective as boosters, regardless of primary series (Healio) - "This is a tour-de-force study, and it supports the mix-and-match approach. It also suggests that, regardless of what COVID-19 vaccine you received first — with the possible exception of CureVac — an mRNA booster is best."

Online posting • Novel Coronavirus Disease

Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. (PubMed, Lancet) - "All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination."

Clinical • Journal • P2 data • Fatigue • Infectious Disease • Meningococcal Infections • Novel Coronavirus Disease • Pain • Respiratory Diseases

A Dose-Confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults for COVID-19 (clinicaltrials.gov) - P2a; N=674; Active, not recruiting; Sponsor: CureVac AG; Trial completion date: Nov 2021 ➔ Feb 2022; Trial primary completion date: Nov 2021 ➔ Feb 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR