A comparative study between vaccines against Covid-19 in phase III clinical trials/ Um estudo comparativo entre vacinas contra Covid-19 em ensaios clínicos de fase III

Authors

  • Carolina Dourado de Faria
  • Fernando Antônio Ramos Schramm Neto
  • Yuri de Jesus Machado
  • Rafael Alves dos Santos e Santos
  • Luna Brenda Carvalho Abade Moura Batista
  • Carla Jaqueline Silva Sampaio
  • Rosane Dantas Santiago
  • José Fierre Esteves
  • Ramon Andrade de Souza
  • Roberto de Barros Silva

DOI:

https://doi.org/10.34119/bjhrv4n6-282

Keywords:

SARS-CoV-2, Vaccine-Preventable Diseases, Public Health.

Abstract

Objective: Compare different characteristics of the vaccines against Covid-19 in phase III clinical trials: type of vaccine, storage, route of administration, number of doses, interval between doses, countries tested, age group tested, seroconversion interval, general efficacy, country distribution, estimated number of participants, and pharmacodynamics. Methods: Phase III clinical trials were identified through the ClinicalTrials.gov database. The filters used were: coronavirus infection; vaccines; clinical trials; all studies; recruitment status (all); stage III; 06-06-2020 to 06-06-2021. 182 studies were found. After excluding studies with drug therapies and vaccines not exclusive to Covid-19, there remained 56 studies. Results: Our study compared 28 vaccines in phase III clinical trials. All vaccines with available data on general efficacy achieved values above 50%. More than half of the studies had at least 50,000 participants. The immunizing agents were tested in 37 countries and the predominant age group tested was >=18 years. As for storage 80% of vaccines with available data need to be refrigerated between 2-8 °C, while mRNA type vaccines require lower temperatures.  Regarding types of vaccines, recombinant viral vectors constituted 50%. Within the vaccines approved for distribution, 7.14% were distributed to over 100 countries, in contrast, another 14.29% of the vaccines were distributed to only 1 country each. Conclusion: The analysis and understanding of our results can contribute to disseminate important information so that people do not perceive in a false manner that one vaccine works better than the other, reducing vaccine hesitancy. However, it is up to each nation to compare each immunizer and define the best choice that fits their needs.

References

Velavan TP, Meyer CG. The COVID‐19 epidemic. Tropical medicine & international health. 2020; 25(3): 278.

World Health Organization [internet]. Coronavirus disease (‎COVID-19) [accessed July 23, 2021]. Available: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

New York Times [internet]. Coronavirus in the World: Latest Map and Case Count [accessed July 06, 2021]. Available: https://www.nytimes.com/interactive/2021/world/covid-cases.html.

Iwasaki A, Omer SB. Why and how vaccines work. Cell. 2020; 183(2): 290-295.

Lurie N, Saville M, Hatchett R, Halton J. Developing Covid-19 vaccines at pandemic speed. New England Journal of Medicine. 2020; 382(21): 1969-1973.

Al-Kassmy J, Pedersen J, Kobinger G. Vaccine candidates against Coronavirus infections. Where Does COVID-19 stand?. Viruses. 2020; 12(8): 861.

Tregoning JS, Brown ES, Cheeseman HM, Flight KE, Higham SL, Lemm NM et al. Vaccines for COVID‐19. Clinical & Experimental Immunology. 2020; 202(2): 162-192.

Ng WH, Liu X, Mahalingam S. Development of vaccines for SARS-CoV-2. F1000Research. 2020; 9.

Healthydebate [internet]. Comparing vaccines: efficacy, safety and side effects [accessed July 08, 2021]. Available: https://healthydebate.ca/2021/03/topic/comparing-vaccines/.

Mathieu E, Ritchie H, Ortiz-Ospina E, Roser M, Hasell J, Appel C. et al. A global database of COVID-19 vaccinations. Nature human behaviour. 2021; 1-7.

Kreps S, Prasad S, Brownstein JS, Hswen Y, Garibaldi BT, Zhang B et al. Factors associated with US adults’ likelihood of accepting COVID-19 vaccination. JAMA network open 2020; 3(10): e2025594-e2025594.

Sherman SM, Smith LE, Sim J, Amlôt R, Cutts M, Dasch H. et al. COVID-19 vaccination intention in the UK: results from the COVID-19 vaccination acceptability study (CoVAccS), a nationally representative cross-sectional survey. Human vaccines & immunotherapeutics. 2021; 17(6): 1612-1621.

Vox [internet]. Why comparing Covid-19 vaccine efficacy numbers can be misleading [accessed July 08, 2021]. Available: https://www.vox.com/22311625/covid-19-vaccine-efficacy-johnson-moderna-pfizer.

EitHealth [internet]. Are COVID-19 vaccine trial results understood? [accessed July 08, 2021]. Available: https://eithealth.eu/view/are-covid-19-vaccine-trial-results-understood-and-why-does-it-matter/.

PanAmerican Health Organization. Introduction and Implementation of New Vaccines: Field Guide. Washington, DC: OPS, 2009.

World Health Organization [internet]. Vaccine efficacy, effectiveness and protection [accessed July 23, 2021]. Available: https://www.who.int/news-room/feature-stories/detail/vaccine-efficacy-effectiveness-and-protection.

Clemens J, Brenner R, Rao M, Tafari N, Lowe C. Evaluating new vaccines for developing countries: efficacy or effectiveness?. Jama. 1996; 275(5): 390-397.

UsaToday [internet]. Comparing the COVID-19 vaccines [accessed July 23, 2021]. Disponible: https://www.usatoday.com/in-depth/graphics/2021/03/27/comparing-covid-19-vaccines/6806600002/.

World Health Organization [internet]. What is COVID-19 vaccine efficacy? [accessed July , 2021]. Available: https://www.afro.who.int/news/what-covid-19-vaccine-efficacy.

Marrugat J, Vila J, Elosua R. Is it appropriate to compare the results from two clinical trials with one drug in common?. Revista espanola de cardiologia (English ed.). 2013; 66(2): 151-153.

Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. bmj. 2020; 369.

EitHealth [internet]. Are COVID-19 vaccine trial results understood? [accessed July 23, 2021]. Available: https://eithealth.eu/view/are-covid-19-vaccine-trial-results-understood-and-why-does-it-matter/.

National Institutes of Health [internet]. Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released [accessed July 23, 2021]. Available: https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released.

Food and Drug Administration. Janssen COVID-19 Vaccine EUA Fact Sheet for Healthcare Providers - Janssen COVID-19 Vaccine EUA Fact Sheet for Healthcare Providers. Available: https://www.fda.gov/media/146304/download.

Janssen Biotech, Inc. Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. FDA Briefing Document. February 26, 2021. Available at: https://www.fda.gov/media/146217/download.

dos Reis RP, Leite JGR, Costa GA. Vacinas contra Covid-19: o que podemos dizer nesse momento?.

CNNBrasil [internet]. É pouco provável que vacinas não sejam seguras a crianças, dizem especialistas [accessed July 26, 2021]. Available: https://www.cnnbrasil.com.br/saude/2021/02/13/testes-de-vacina-em-criancas-comecam-com-imunizante-ja-usado-em-adultos.

Centers for Disease Control and Prevention [internet]. Ensuring the Safety of Vaccines in the United States [accessed July 26, 2021]. Available: https://www.cdc.gov/vaccines/hcp/conversations/ensuring-safe-vaccines.html.

Johns Hopkins Medicine [internet]. COVID-19 Vaccine: What Parents Need to Know [accessed July 26, 2021]. Available: https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/covid19-vaccine-what-parents-need-to-know.

Centers for Disease Control and Prevention [internet]. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States [accessed July 26, 2021]. Available: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.

World Health Organization et al. COVID-19 vaccination: supply and logistics guidance: interim guidance. World Health Organization. 2021. 76 p.

Centers for disease control and prevention. Vaccine Storage and Handling Toolkit. Centers for disease control and prevention. 2021. 65 p.

Ministry of Health [internet]. COVID-19: Vaccine Storage and Handling Guidance [accessed July 26, 2021]. Available: https://www.health.gov.on.ca/en/pro/programs/publichealth/coronavirus/docs/vaccine/vaccine_storage_handling_pfizer_moderna.pdf.

The Times of India [internet]. World’s ‘best’ vaccines could soon come to poor countries [accessed July 26, 2021]. Available: https://timesofindia.indiatimes.com/india/worlds-best-vaccines-could-soon-come-to-poor-countries/articleshow/82512515.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst.

Park JW, Lagniton PN, Liu Y, Xu RH. mRNA vaccines for COVID-19: what, why and how. International journal of biological sciences. 2021; 17(6): 1446.

Yan Y, Pang Y, Lyu Z, Wang R, Wu X, You C et al.. The COVID-19 vaccines: recent development, challenges and prospects. Vaccines. 2021; 9(4): 349.

Crommelin DJ, Anchordoquy TJ, Volkin DB, Jiskoot W, Mastrobattista E. Addressing the cold reality of mRNA vaccine stability. Journal of Pharmaceutical Sciences. 2021; 110(3): 997-1001.

Peiris M, Leung GM. What can we expect from first-generation COVID-19 vaccines?. Lancet (London, England). 2020; 396(10261): 1467.

Chen JM. Live unattenuated vaccines for controlling viral diseases, including COVID‐19. Journal of Medical Virology. 2021; 93(4): 1943-1949.

Reichmuth AM, Oberli MA, Jaklenec A, Langer R, Blankschtein D. mRNA vaccine delivery using lipid nanoparticles. Therapeutic delivery. 2016; 7(5): 319-334.

Curevac [internet]. CureVac’s COVID-19 Vaccine Candidate, CVnCoV, Suitable for Standard Fridge Temperature Logistics [accessed July 26, 2021]. Available: https://www.curevac.com/en/2020/11/12/curevacs-covid-19-vaccine-candidate-cvncov-suitable-for-standard-fridge-temperature-logistics/.

Precision vaccinations [internet]. INO-4800 COVID-19 Vaccine [accessed July 26, 2021]. Available: https://www.precisionvaccinations.com/vaccines/ino-4800-covid-19-vaccine.

Kristensen DD, Lorenson T, Bartholomew K, Villadiego S. Can thermostable vaccines help address cold-chain challenges? Results from stakeholder interviews in six low-and middle-income countries. Vaccine. 2016; 34(7): 899-904.

Mammen MP, Tebas P, Agnes J, Giffear M, Kraynyak KA, Blackwood E et al. Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of a randomized, blinded, placebo-controlled, Phase 2 clinical trial in adults at high risk of viral exposure. medRxiv. 2021.

Zuckerman JN. The importance of injecting vaccines into muscle: different patients need different needle sizes. 2000.

Poland GA, Borrud A, Jacobson RM, McDermott K, Wollan PC, Brakke D et al. Determination of deltoid fat pad thickness: implications for needle length in adult immunization. Jama. 1997; 277(21): 1709-1711.

Revista Galileu [internet]. Por que tomamos vacinas no braço? [accessed July 26, 2021]. Available: https://revistagalileu.globo.com/Ciencia/Saude/noticia/2021/05/por-que-tomamos-vacinas-no-braco.html.

University Health Network, Toronto. Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 (COVID-19) Infection Rate and Severity (COBRA). ClinicalTrials. gov: NCT04439045. 2020.

Vakzine Projekt Management GmbH. Study to Assess VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in COVID-19 Pandemic. ClinicalTrials. gov: NCT04435379. 2020.

Bricks LF. Percutaneous or intradermal BCG vaccine?. Jornal de pediatria. 2004; 80: 93-98.

Inovio Pharmaceuticals. Safety, Immunogenicity, and Efficacy of INO-4800 for COVID-19 in Healthy Seronegative Adults at High Risk of SARS-CoV-2 Exposure. ClinicalTrials. gov: NCT04642638. 2020.

Haidari G, Cope A, Miller A, Venables S, Yan C, Ridgers H et al. Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial. Scientific reports. 2017; 7(1): 1-11.

Park JH, Lee HK. Delivery Routes for COVID-19 Vaccines. Vaccines. 2021; 9(5): 524.

British Society for Immunology [internet]. Why do we need multiple doses of a vaccine? [accessed July 26, 2021]. Available: https://www.immunology.org/coronavirus/connect-coronavirus-public-engagement-resources/why-multiple-doses-covid19-vaccine.

Livingston EH. Necessity of 2 doses of the Pfizer and Moderna COVID-19 vaccines. JAMA. 2021; 325(9): 898-898.

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine. 2020.

Wall EC, Wu M, Harvey R, Kelly G, Warchal S, Sawyer C. et al. Neutralising antibody activity against SARS-CoV-2 VOCs B. 1.617. 2 and B. 1.351 by BNT162b2 vaccination. The Lancet. 2021; 397(10292): 2331-2333.

Johnson & Johnson [internet]. Johnson & Johnson COVID-19 Vaccine Authorized by U.S. FDA For Emergency Use - First Single-Shot Vaccine in Fight Against Global Pandemic [accessed July 26, 2021]. Available: https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic.

Nature [internet]. Mounting evidence suggests Sputnik COVID vaccine is safe and effective [accessed July 26, 2021]. Available: https://www.nature.com/articles/d41586-021-01813-2.

Sputnik Vaccine [internet]. Single dose vaccine, Sputnik Light, authorized for use in Russia [accessed July 26, 2021]. Available: https://sputnikvaccine.com/newsroom/pressreleases/single-dose-vaccine-sputnik-light-authorized-for-use-in-russia/.

Wu S, Zhong G, Zhang J, Shuai L, Zhang Z, Wen Z et al. A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge. Nature communications. 2020; 11(1): 1-7.

Andreadakis Z, Kumar A, Román RG, Tollefsen S, Saville M, Mayhew S. The COVID-19 vaccine development landscape. Nature reviews. Drug discovery. 2020; 19(5): 305-306.

Folha de São Paulo [internet]. Veja quais são os intervalos entre as doses das vacinas contra Covid no Brasil e por que eles são diferentes [accessed July 26, 2021]. Available: https://www1.folha.uol.com.br/equilibrioesaude/2021/05/veja-quais-sao-os-intervalos-entre-as-doses-das-vacinas-contra-covid-no-brasil-e-por-que-eles-sao-diferentes.shtml.

Sociedade Brasileira de Imunizações [internet]. Nota Técnica Conjunta SBIm/SBP: intervalo entre as doses das vacinas COVID-19 AstraZeneca/Oxford e Pfizer – 13/07/2021 [accessed July 26, 2021]. Available: https://sbim.org.br/images/files/notas-tecnicas/nota-tecnica-sbim-sbp-intervalo-vacinas-oxford-pfizer.pdf.

Mahase E. Covid-19: One dose of vaccine cuts risk of passing on infection by as much as 50%, research shows. 2021.

Bernal JL, Andrews N, Gower C, Robertson C, Stowe J, Tessier E et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. bmj. 2021; 373.

Immunize.org [internet]. The importance of minimum ages and intervals in the vaccine schedule [accessed July 26, 2021]. Available: https://www.immunize.org/catg.d/s8025.pdf.

Medical News Today [internet]. Longer gap between COVID-19 vaccine doses may increase immune response [accessed July 26, 2021]. Available: https://www.medicalnewstoday.com/articles/longer-gap-between-covid-19-vaccine-doses-may-increase-immune-response#Encouraging-results.

Sociedade Brasileira de Análises Clínicas [internet]. COVID-19 – Conhecendo o inimigo [accessed July 26, 2021]. Available: https://www.sbac.org.br/blog/2020/04/16/covid-19-conhecendo-o-inimigo/.

Yan ZP, Yang M, Lai CL. COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials. Pharmaceuticals. 2021; 14(5): 406.

Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA et al. Author Correction: Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 588(7839): E35-E35.

Serrano-Barrera OR. Análisis filogenético del receptor humano del coronavirus SARS-CoV-2 e implicaciones en la biología de la infección. Revista Electrónica Dr. Zoilo E. Marinello Vidaurreta. 2020; 45(3).

Amanat F, Stadlbauer D, Strohmeier S, Nguyen TH, Chromikova V, McMahon M et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nature medicine. 2020; 26(7): 1033-1036.

Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nature medicine. 2020; 26(6): 845-848.

StatNews [internet]. Comparing the Covid-19 vaccines developed by Pfizer, Moderna, and Johnson & Johnson [accessed July 26, 2021]. Available: https://www.statnews.com/2021/02/02/comparing-the-covid-19-vaccines-developed-by-pfizer-moderna-and-johnson-johnson/.

Rede São Luiz [internet]. Tipos de vacina contra a COVID 19: o que temos aprovado para uso no Brasil [accessed July 26, 2021]. Available: https://www.rededorsaoluiz.com.br/noticias/artigo/tipos-de-vacina-contra-a-covid-19-o-que-temos-aprovado-para-uso-no-brasil.

World Health Organization [internet]. Os diferentes tipos de vacinas COVID-19 [accessed July 26, 2021]. Available: https://www.who.int/pt/news-room/feature-stories/detail/the-race-for-a-covid-19-vaccine-explained.

Nature [internet]. How COVID vaccines are being divvied up around the world [accessed July 26, 2021]. Available: https://www.nature.com/articles/d41586-020-03370-6.

Duke [internet]. Will Low-Income Countries Be Left Behind When COVID-19 Vaccines Arrive? [accessed July 26, 2021]. Available: https://globalhealth.duke.edu/news/will-low-income-countries-be-left-behind-when-covid-19-vaccines-arrive.

World Health Organization [internet]. Vaccine inequity undermining global economic recovery[accessed July 26, 2021]. Available: https://www.who.int/news/item/22-07-2021-vaccine-inequity-undermining-global-economic-recovery.

University of Oxford [internet]. Oxford University breakthrough on global COVID-19 vaccine [accessed July 26, 2021]. Available: https://www.ox.ac.uk/news/2020-11-23-oxford-university-breakthrough-global-covid-19-vaccine.

ReliefWeb [internet]. Unequal Vaccine Distribution Self-Defeating, World Health Organization Chief Tells Economic and Social Council’s Special Ministerial Meeting [accessed July 26, 2021]. Available: https://reliefweb.int/report/world/unequal-vaccine-distribution-self-defeating-world-health-organization-chief-tells.

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Published

12/07/2021

How to Cite

FARIA, C. D. de; NETO, F. A. R. S.; MACHADO, Y. de J.; SANTOS, R. A. dos S. e; BATISTA, L. B. C. A. M.; SAMPAIO, C. J. S.; SANTIAGO, R. D.; ESTEVES, J. F.; SOUZA, R. A. de; SILVA, R. de B. A comparative study between vaccines against Covid-19 in phase III clinical trials/ Um estudo comparativo entre vacinas contra Covid-19 em ensaios clínicos de fase III. Brazilian Journal of Health Review, [S. l.], v. 4, n. 6, p. 27138–27165, 2021. DOI: 10.34119/bjhrv4n6-282. Disponível em: https://ojs.brazilianjournals.com.br/ojs/index.php/BJHR/article/view/40746. Acesso em: 19 oct. 2026.

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Original Papers