Summary
Background
Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate.
Methods
Findings
Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0–61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5–86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18–60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2–64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group.
Interpretation
CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates.
Funding
German Federal Ministry of Education and Research and CureVac.
Introduction
WHO coronavirus (COVID-19) dashboard.
Through unprecedented effort from governments, national and international research funders, regulatory bodies, and research organisations, vaccine development has been, and continues to be, expedited. The first conditionally approved vaccine in Europe was administered in December, 2020, within 9 months of WHO characterising COVID-19 as a pandemic on March 11, 2020.
WHO Director-General’s opening remarks at the media briefing on COVID-19—11 March 2020.
The COVID-19 vaccine race—weekly update.
These vaccines have been developed by use of different platforms, all with specific advantages and disadvantages.
mRNA is a promising platform that allows the rapid development of immunogens and vaccine production.
- Pardi N
- Hogan MJ
- Porter FW
- Weissman D
,
- Jackson NAC
- Kester KE
- Casimiro D
- Gurunathan S
- DeRosa F
The BNT162b2 (Pfizer-BioNtech) and mRNA-1273 (Moderna) SARS-CoV-2 vaccines were the first mRNA preventive vaccines to be approved for emergency use in humans in Europe and the USA on the basis of data from phase 3 efficacy trials.
- Polack FP
- Thomas SJ
- Kitchin N
- et al.
,
- Baden LR
- El Sahly HM
- Essink B
- et al.
- Rauch S
- Roth N
- Schwendt K
- Fotin-Mleczek M
- Mueller SO
- Petsch B
,
- Rauch S
- Gooch K
- Hall Y
- et al.
In a phase 1 dose-escalation study, two doses of CVnCoV administered 28 days apart were safe and immunogenic, with dose-dependent increases in anti-spike protein IgG antibodies and SARS-CoV-2-neutralising antibodies.
- Kremsner PG
- Mann P
- Kroidl A
- et al.
Median antibody titres against spike protein and its receptor binding domain after two 12 μg doses of CVnCoV were similar to those observed in convalescent serum samples from patients with COVID-19, with seroconversion observed 2 weeks after the second dose in all participants receiving this dosage. On the basis of these findings, the 12 μg dose was selected for further phase 2/3 testing. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in a phase 2b/3 trial.
Evidence before this study
We searched PubMed for clinical trials published between Jan 1, 2019, and Sept 19, 2021, without language restrictions, using the terms ‘SARS-CoV-2’ OR ‘COVID-19’ AND ‘Vaccine’ AND ‘Efficacy’. At the time of the search, we identified 12 peer-reviewed publications of phase 2/3 and phase 3 clinical trials reporting the efficacy of COVID-19 vaccines in different populations. We did not consider press releases or preprints as sources of information. Eight primary publications reported vaccine efficacies ranging from 62% to 95%. The mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNtech) mRNA vaccines have shown 94% and 95% efficacy, respectively, in preventing COVID-19, with cases accrued at a time when no circulating variants had been identified. Variant-dependent differences in vaccine efficacy have been reported, with reductions in efficacy of up to 60 percentage points against newly emerged SARS-CoV-2 variants of concern.
Added value of this study
We report the primary efficacy analysis of the CVnCoV mRNA vaccine candidate from the phase 2b/3 HERALD trial that comprised 39 680 participants from ten countries in Europe and Latin America. CVnCoV had an acceptable safety profile. Solicited adverse events were common, and more frequently reported in the CVnCoV group than in the placebo group, but the median duration of grade 3 solicited adverse events was 1 day. CVnCoV was 48·2% efficacious in the prevention of COVID-19 of any severity in a variant-dominated setting. Indeed, only seven (3%) of all 204 sequenced COVID-19 cases were of B.1 lineage, with the others caused by 14 different variants. In Europe, 45 (92%) of 49 cases were caused by the alpha variant of concern (B.1.1.7), compared with Latin America where 20 (13%) of 155 cases were caused by the alpha variant and 35 (23%) cases were caused by the gamma variant of concern (P.1).
Implications of all the available evidence
In view of the changing environment, including the emergence of SARS-CoV-2 variants, and taking into account timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the promising and rapidly progressing development of next-generation vaccine candidates. In addition, it might be necessary to consider alternative designs for future global efficacy trials given the number of rapidly emerging SARS-CoV-2 variants and the high uptake of COVID-19 vaccines under emergency use authorisation.
Methods
Study design and participants
The initial phase 2b part of the trial was designed to characterise the safety, reactogenicity, and immunogenicity of the CVnCoV vaccine candidate, and the phase 3 part of the trial was designed to evaluate its efficacy and safety. The two parts of the trial were designed to allow participants with COVID-19 accrued in the phase 2b part of the trial to be pooled with those in the phase 3 part of the trial for the primary analysis of vaccine efficacy. An independent data and safety monitoring board (DSMB) conducted interim safety reviews of the phase 2b part of the trial before enrolment for the phase 3 part of the trial was initiated and will continue to monitor safety until study end. An enrolment target was that 20–25% of the population would be aged 61 years or older. We planned to enrol the first 4000 participants in the phase 2b part of the trial and to include the first 600 participants in each age group in the assessment of immunogenicity endpoints. The DSMB reviewed the safety data when approximately 1800 participants (900 in both treatment groups) had been enrolled in the phase 2b part of the trial and had at least 1 week of safety follow-up after the first dose. Enrolment of participants into the phase 3 part of the trial would begin without interruption from the phase 2b part of the trial if the safety profile was considered acceptable. The DSMB also reviewed all safety data after all participants in each group in the phase 2b trial had received their second trial vaccination and had at least 1 week of safety follow-up.
The trial protocol and its amendments received ethics approval from the appropriate independent ethics committees or institutional review boards at each study centre. The trial is being conducted in accordance with the provisions of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. All participants provided written informed consent before initiation of any trial procedures.
Randomisation and masking
Trial participants were randomly assigned (1:1) to receive either CVnCoV or placebo. Randomisation, stratified by country and age group (18–60 years and ≥61 years), was done centrally by use of an interactive web response system. The randomisation scheme was generated and managed by an independent statistics group at the contract research organisation, PRA. Due to the difference in appearance and presentation between the CVnCoV vaccine candidate and placebo, site personnel involved in preparing the vaccine masked the content of the syringe with a label and were not involved in further conduct of the trial. Investigators, site personnel, and others directly involved in the conduct of the trial were masked to participant allocation for the duration of the trial. The statisticians analysing the data were masked to group assignment until the final analyses. Unmasking of participants was allowed in emergency situations for reasons of participant safety or for participants who became eligible to receive an authorised SARS-CoV-2 vaccine and requested unmasking.
Procedures
Participants in both the phase 2b and the phase 3 parts of the trial received either two 0·6 mL doses of CVnCoV containing 12 μg of mRNA, formulated with the RNActive mRNA vaccine platform, or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. Each 0·6 mL dose was administered by intramuscular injection in the deltoid area. Blood samples (6 mL) were taken from all participants on day 1 and day 43 (14 days after the second dose) and will be taken on day 211 and day 393 (study end) to measure SARS-CoV-2 nucleocapsid protein serostatus. The samples were sent to one of two central laboratories in the USA or the Netherlands and tested with the Elecsys assay on the COBAS system (Roche Diagnostics; Mannheim, Germany). The results on day 1 and day 43 identified whether participants were naive to SARS-CoV-2 infection at trial entry and 15 days after the second vaccination, and were therefore eligible for inclusion in the efficacy analysis subset.
US Food and Drug Administration. Development and licensure of vaccines to prevent COVID-19. Guidance for industry.
and participants were contacted twice per week by site staff via a mobile application to respond yes or no to having potential COVID-19 symptoms. Site personnel then contacted participants who replied yes to ascertain whether their symptoms were indicative of COVID-19 by following a scripted interview. Upon suspicion of COVID-19, participants underwent a rapid antigen test (Abbott Panbio COVID-19 Ag Rapid Test; Jena, Germany) to allow them to comply with local quarantine rules if the results were positive. In addition, samples were sent to central laboratories for SARS-CoV-2-specific RT-PCR testing (In-house test, with probes and primers from Eurofins [Louisville KY, USA]; Latin America testing done in Lancaster [PA, USA]; European testing done in Breda [Netherlands]) for virological confirmation of COVID-19. In case of discrepancies between tests, the RT-PCR test result was considered definitive. All primary efficacy cases were confirmed by an independent adjudication committee. Sequencing of the complete viral single stranded RNA genome was carried out using Illumina Next Generation Sequencing (Viracor-Eurofins, Lee’s Summit, MO, USA).
US Food and Drug Administration. COVID-19: developing drugs and biological products for treatment or prevention. Guidance for industry.
Outcomes
The primary efficacy outcome was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose up to 1 year. The primary outcome was assessed by a blinded, central adjudication committee. Key secondary efficacy outcomes included the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, and the occurrence of a first episode of virologically confirmed severe COVID-19, overall and by age group (18–60 years vs ≥61 years). An exploratory efficacy endpoint, which was added in the protocol amendment on March 29, 2021, was the occurrence of a first episode of virologically confirmed COVID-19 caused by an individual variant of concern or interest.
Statistical analysis
HERALD is an event-driven trial, and sample size and power considerations were based on the primary objective of showing the efficacy of CVnCoV in preventing virologically confirmed cases of COVID-19 of any severity meeting the primary case definition. Assuming a vaccine efficacy of 60%, with an overall two-sided α of 5%, we estimated that 160 participants with COVID-19 of any severity, with a third of cases being moderate to severe, were needed for the final analysis to have a power of 90% to show a vaccine efficacy of more than 30% based on the lower bound of the CI for efficacy. Assuming a COVID-19 incidence of 0·15% per month in participants in the placebo group, an overall non-evaluable proportion of 20% (corresponding to participants excluded from the efficacy analysis set and those who dropped out), and a vaccine efficacy of 60%, we estimated that 36 500 participants (18 250 per group) enrolled over approximately 3 months would accrue 160 COVID-19 cases of any severity at approximately 9 months after the first vaccination.
During case accrual, before the second interim analysis was done, we observed that the actual proportion of participants with moderate-to-severe COVID-19 was approximately 20%, which was lower than the expected 30%. The protocol was amended to allow accrual of more cases to obtain the planned sample size (about 53 participants with moderate-to-severe COVID-19) needed for the key secondary endpoint of measuring vaccine efficacy against moderate-to-severe COVID-19.
Vaccine efficacy against symptomatic disease was analysed in the primary efficacy analysis set, which comprised all participants in the phase 2b and phase 3 parts of the trial who received both doses of either CVnCoV or placebo according to their treatment allocation, had not developed virologically confirmed COVID-19 before day 43 (15 days after the second dose), and were SARS-CoV-2-naive at baseline and day 43. Vaccine efficacy was defined as 1 minus the ratio of the attack rate in participants receiving CVnCoV to participants receiving placebo, multiplied by 100. In each group, the attack rate was defined as the number of participants presenting with virologically confirmed COVID-19 divided by the total follow-up time. For the primary analysis, the hypothesis was tested with the exact test for binomial proportions. The trial was considered successful if the lower limit of the exact two-sided Clopper-Pearson 95% CI (subject to adjustment for multiple testing according to the cumulative O’Brien-Fleming type error spending function, giving an actual CI of 95·826%) of the primary efficacy endpoint (COVID-19 cases of any severity) was more than 30%. Success for key secondary endpoints was defined as the lower limit of the exact two-sided 95% CI being more than 20% for moderate-to-severe disease, and more than 10% for severe disease. Kaplan-Meier curves and associated log-rank tests were done in a key prespecified sensitivity analysis to evaluate time to first occurrence of virologically confirmed COVID-19. Post-hoc, we evaluated vaccine efficacy by region.
Role of the funding source
CureVac was responsible for trial design and conduct, data analysis, data interpretation, and writing of the report. The German Federal Ministry of Education and Research had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Results
Table 1Baseline and day 43 characteristics in the phase 2b–3 safety analysis set
Data are n (%), median (IQR), or n/N (%). The phase 2b–3 safety analysis set comprises all participants who received at least one dose of CVnCoV or placebo, who are analysed in the group of the treatment dose received. BMI=body-mass index.
Table 2Efficacy of CVnCoV against virologically confirmed COVID-19 occurring 15 days or more after the second dose in the primary efficacy analysis set
Tracking SARS-CoV-2 variants.
In Europe, 45 (92%) of 49 cases were caused by the alpha variant (the remaining four cases were caused by the gamma variant [P.1; two], by the delta variant [B.1.617.2; one], and by an unidentified variant at the time [one]). In Latin America, 20 (13%) of 155 cases were caused by the alpha variant, 34 (22%) were caused by the gamma variant, 43 (28%) were caused by the lambda variant of interest (C.37), and 29 (19%) were caused by the Mu variant of interest (B.1.621). The remaining cases were caused by alpha (20 [13%]), B.1.526 (iota; one [1%]), wild-type (seven [5%]), P.2 (zeta; one [1%]), and other (20 [13%]). Vaccine efficacies against the alpha, gamma, and lambda variants in people aged 18–60 years were similar to the overall efficacy (table 2).
Table 3Adverse events
Data are n/N (%) or n/N (%); number of events. Serious adverse events are reported from immediately after the second dose to the date of data cutoff (June 18, 2021).
Discussion
Considerations for evaluation of COVID19 vaccines.
Vaccine efficacy against COVID-19 of any severity was 48·2% (95·826% CI 31·0–61·4) in the overall primary efficacy analysis set of SARS-CoV-2-naive participants, and 52·5% (95% CI 36·2–64·8) in those aged 18–60 years. Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (42·5–86·1) overall and 77·2% (51·8–90·4) in participants aged 18–60 years. There were too few participants aged 61 years or older who developed COVID-19 to allow a meaningful estimate of efficacy in this age group.
- Polack FP
- Thomas SJ
- Kitchin N
- et al.
,
- Baden LR
- El Sahly HM
- Essink B
- et al.
No increase in solicited reactions was seen between the first and second CVnCoV doses. Serious adverse events and adverse events of special interest were uncommon and similar in frequency between the CVnCoV and placebo groups, although the short follow-up duration needs to be considered when interpreting these findings. The safety of the CVnCoV vaccine candidate will continue to be monitored for the duration of the trial, and findings will be presented in a future publication. Taken together with the safety data from phase 1 trials with CVnCoV and with the CV7202 rabies mRNA vaccine,
- Kremsner PG
- Mann P
- Kroidl A
- et al.
,
- Aldrich C
- Leroux-Roels I
- Huang KB
- et al.
the findings observed in this trial provide further support for the safety of the RNActive mRNA vaccine platform.
- Rauch S
- Lutz J
- Kowalczyk A
- Schlake T
- Heidenreich R
Tracking SARS-CoV-2 variants.
Although we were only able to evaluate vaccine efficacy against these variants in participants aged 18–60 years, the results indicate that the vaccine had similar efficacies against alpha, gamma, and lambda variants. Many newly emerged strains have shown increased transmissibility,
- Hossain MK
- Hassanzadeganroudsari M
- Apostolopoulos V
and differences in neutralising antibody activity against these strains might alter vaccine efficacy.
- Garcia-Beltran WF
- Lam EC
- St Denis K
- et al.
These concerns are supported by results from other phase 3 efficacy trials, with SARS-CoV-2 variant-dependent differences in efficacy reported for the ChAdOx1 nCoV-19 (Oxford-AstraZeneca),
- Voysey M
- Clemens SAC
- Madhi SA
- et al.
,
- Emary KRW
- Golubchik T
- Aley PK
- et al.
,
- Madhi SA
- Baillie V
- Cutland CL
- et al.
NVX-CoV2373 (Novavax),
- Heath PT
- Galiza EP
- Baxter DN
- et al.
,
- Shinde V
- Bhikha S
- Hoosain Z
- et al.
and Ad26.COV2.S (Janssen) SARS-CoV-2 vaccines.
- Sadoff J
- Gray G
- Vandebosch A
- et al.
The point estimates for real-world mRNA vaccine effectiveness, in settings with increasing diversity of variants, are lower than the point estimates for efficacy as reported in clinical trials.
- Kustin T
- Harel N
- Finkel U
- et al.
,
- Puranik A
- Lenehan PJ
- Silvert E
- et al.
,
- Nasreen S
- He S
- Chung H
- et al.
In this context, the comparison of vaccine efficacy against different SARS-CoV-2 variants and between Europe and Latin America, although not prespecified in the protocol, is important from a public health perspective. Broad geographical representation should therefore be considered when designing future studies evaluating the efficacy of SARS-CoV-2 vaccines and vaccine efficacy against emerging variants.
- Polack FP
- Thomas SJ
- Kitchin N
- et al.
,
- Baden LR
- El Sahly HM
- Essink B
- et al.
,
- Voysey M
- Clemens SAC
- Madhi SA
- et al.
,
- Heath PT
- Galiza EP
- Baxter DN
- et al.
,
- Sadoff J
- Gray G
- Vandebosch A
- et al.
The low recruitment, combined with the large number of older participants who were unmasked and therefore contributed less follow-up time to the efficacy analyses, limited the interpretability of our findings in this age group and affected the overall study results.
- Polack FP
- Thomas SJ
- Kitchin N
- et al.
,
- Baden LR
- El Sahly HM
- Essink B
- et al.
,
- Heath PT
- Galiza EP
- Baxter DN
- et al.
,
- Sadoff J
- Gray G
- Vandebosch A
- et al.
The clinical implications of CVnCoV’s 70·7% efficacy against moderate-to-severe COVID-19, nearly all cases of which were caused by variants of concern or variants of interest, suggest a high potential for a positive impact on public health. Access to vaccines protecting against moderate-to-severe disease, and thus preventing disruption to the normal functioning of hospitals and intensive care units, is essential to prevent non-COVID-19-associated morbidity and mortality.
- Berg GM
- Wyse RJ
- Morse JL
- et al.
,
- Woolf SH
- Chapman DA
- Sabo RT
- Weinberger DM
- Hill L
- Taylor DDH
,
- Dopfer C
- Wetzke M
- Zychlinsky Scharff A
- et al.
- Kremsner PG
- Mann P
- Kroidl A
- et al.
However, in view of the changing environment, including the emergence of SARS-CoV-2 variants, and taking into account timelines for further development, the decision had been made to cease activities on the CVnCoV candidate, and to focus efforts on the promising and rapidly progressing development of the next generation vaccine candidates. One of these, the CV2CoV candidate, has already been shown to induce high humoral and cellular immune responses in non-human primate studies.
- Gebre MS
- Rauch S
- Roth N
- et al.
In conclusion, the two-dose regimen of CVnCoV had an acceptable safety profile and was efficacious in the prevention of symptomatic COVID-19 in adults. In addition, we observed vaccine efficacy against newly emerged variants, including variants of concern.
Contributors
PGK, AK, IL-R, PM, OS-K, TV, and LO conceived the HERALD trial; PGK is the coordinating investigator and LO is study lead. HJ is the qualified physician and co-chair of the DSMB. PGK, RC, EJLDB, MAGG, AK, IL-R, PM, MFM-R, OS-K, TV, and LO contributed to the trial design and protocol. PGK, HJ, PM, and TV participated in the data curation and had full access to and verified all study data. PGK, AK, PM, OS-K, TV, and LO did the statistical analyses. PGK, RAAG, EA-A, GJAM, MB, RC, RC GC, EJLDB, LE, JJG, CAGL, LG, MAGG, NG, MPG, ADH, CFL, CL, IL-R, MFM-R, TJO, CAP, MJRF, LMRM, VVRH, XS-L, MS, ASG, IV, and MV are study site principal investigators. PGK, PM, OS-K, and LO were in the core writing group responsible for preparation of the manuscript and received support from a medical writer. Manuscript drafts were reviewed by all authors, and the content of the submitted version was approved by all authors before submission. All authors had final responsibility for the decision to submit for publication. Because the study is ongoing, authors could not be given access to the whole dataset analysed in this Article, but they will be given full access when the study is terminated.
Data sharing
Anonymised participant data will be made available when the trial is complete, on requests directed to the corresponding author. Proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. After approval of a proposal, data can only be shared through a secure online platform after a data access agreement is signed. All data will be made available for a minimum of 5 years from the end of the trial.
Declaration of interests
MB declares institutional funding from CureVac during the conduct of this study, institutional funding from Janssen Vaccines, Molecular Partners, and Merck outside the submitted work, and consulting fees from Janssen Vaccines outside the submitted work. EJLDB, MFM-R, TJO, and XS-L declare institutional funding from CureVac during the conduct of this study. LE and LG declare institutional funding from CureVac during the conduct of this study and outside the submitted work. CFL declares institutional funding from CureVac during the conduct of this study and outside the submitted work and is a member of the WHO Covid-19 Vaccine Effectiveness Working Group and the WHO Product Development for Vaccines Advisory Committee. CL declares institutional funding from CureVac during the conduct of this study and is a member of the German Society of Infection board. IL-R declares institutional funding from CureVac during the conduct of this study and institutional funding from Johnson & Johnson and OSE Immunotherapeutics outside the submitted work. PGK declares institutional funding from CureVac during the conduct of this study and is a member of the scientific advisory board for the HERALD clinical trial. VVRH declares institutional funding from CureVac during the conduct of this study and speakers fees from Gilead outside the submitted work. HJ declares consultant fees from CureVac, is the qualified physician for the HERALD clinical trial, and is co-chair of the DSMB for the HERALD clinical trial. AK and PM are employed by CureVac and hold stock options. OS-K declares consultant fees from CureVac during the conduct of this study and is a member of the DSMB for a CVnCoV phase 1 trial. TV declares consultant fees from CureVac during the conduct of this study, and consultant fees from CureVac, AstraZeneca, Pfizer, Johnson & Johnson, and Moderna outside the submitted work. LO is employed by CureVac and holds stock options and is the holder of a pending patent. All other authors declare no competing interests.
Acknowledgments
This study was funded by the German Federal Ministry of Education and Research ( grant 01KI20703 ) and CureVac. Draft versions of this manuscript were reviewed by Giulia Povellato and Robert Tensen (Medical Affairs Department, CureVac, Frankfurt, Germany). Medical writing services were provided by Jarno Jansen and Margaret Haugh, who also provided editorial support, both funded by CureVac. We thank all study participants for their contribution to HERALD. We also thank all staff at the clinical study centres, the contract research organisations, the laboratories, and in CureVac, who are too numerous to be named but are nonetheless recognised for their tireless work, which is still ongoing. Special thanks go to the members of the DMSB, chaired by Fred Zepp.
Supplementary Material
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Article Info
Publication History
Published: November 23, 2021
Identification
DOI: https://doi.org/10.1016/S1473-3099(21)00677-0
Copyright
© 2021 Elsevier Ltd. All rights reserved.
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Apart from COVID-19-appropriate behaviour, effective vaccine coverage is the single most important intervention needed to control the ongoing SARS-CoV-2 pandemic. Although several vaccines are being used under emergency use authorisation, worldwide vaccination coverage will only be achieved when vaccine availability exceeds vaccine demand. Globally, several prominent institutions, universities, and leading pharmaceutical companies have successfully developed COVID-19 vaccine candidates that have progressed to clinical trials.
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