Vacunas contra la COVID-19

  1. Alberto J. Villena 1
  1. 1 Profesor Catedrático de Universidad jubilado del Área de Biología Celular, Departamento de Biología Molecular, Universidad de León
AmbioCiencias: revista de divulgación

ISSN: 1988-3021

Year of publication: 2021

Issue Title: Número especial sobre coronavirus

Issue: 19

Pages: 73-106

Type: Article

More publications in: AmbioCiencias: revista de divulgación


La pandemia de la COVID-19, causada por el betacoronavirus SARS-CoV-2, ha tenido una importante incidencia sanitaria y socioeconómica, que solo la vacunación masiva ha tenido la capacidad de mitigar. En esta revisión se abordan aspectos fundamentales de la virología del SARS-CoV-2 en relación con las bases inmunológicas de las vacunas antivirales y de las principales tecnologías vacunales de las vacunas contra la COVID-19, con especial atención a las que utilizan las “nuevas tecnologías” vacunales, derivadas de los avances biotecnológicos. Se describen en detalle algunos ejemplos de las vacunas contra la COVID-19 autorizadas por la Organización Mundial de la Salud y las agencias del medicamento de diversos países. Finalmente, se analizan los impactos sanitarios, científicos y sociales que han tenido el desarrollo de estas vacunas.

Bibliographic References

  • Afrough, B., Dowall, S. y Hewson, R., 2019. Emerging viruses and current strategies for vaccine intervention. Clinical and experimental immunology, 196: 157–166.
  • Alhashimi, M., Elkashif, A., Sayedahmed, E. E. y Mittal, S. K., 2021. Nonhuman adenoviral
  • vector-based platforms and their utility in designing next generation of vaccines for infectious diseases. Viruses, 13: 1493.
  • Antonelli, M., Penfold, R. S., Merino, J., Sudre, C. H. et al., 2021. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. The Lancet, S1473-3099(21)004606.
  • Atasheva, S. y Shayakhmetov, D. M., 2016. Adenovirus sensing by the immune system. Current opinion in virology, 21: 109–113.
  • Bahri, P. y Castillon Melero, M., 2018. Listen to the public and fulfil their information interests - translating vaccine communication research findings into guidance for regulators. British journal of clinical pharmacology, 84: 1696–1705.
  • Barrett, P. N., Mundt, W., Kistner, O. y Howard, M. K., 2009. Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines. Expert review of vaccines, 8: 607–618.
  • Beljelarskaya S. N., 2011. Baculovirus expression systems for production of recombinant
  • proteins in insect and mammalian cells. Molecular biology, 45: 123–138.
  • Berger, I. y Schaffitzel, C., 2020. The SARS-CoV-2 spike protein: balancing stability and infectivity. Cell research 30: 1059–1060.
  • Bestle, D., Heindl, M. R., Limburg, H., Van Lam van, T. et al., 2020. TMPRSS2 and furin
  • are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life science alliance, 3: e202000786.
  • Bettini, E. y Locci, M., 2021. SARS-CoV-2 RNAm Vaccines: Immunological mechanism and beyond. Vaccines 9: 147.
  • Bode, C., Zhao, G., Steinhagen, F., Kinjo, T. y Klinman, D. M., 2011. CpG ADN as a vaccine
  • adjuvant. Expert review of vaccines, 10: 499–511.
  • Bos, R., Rutten, L., van der Lubbe, J., Bakkers, M., Hardenberg, G. et al., 2020. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. NPJ vaccines, 5: 91.
  • Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M. et al., 2021. Nanomaterial
  • delivery systems for RNAm vaccines. Vaccines, 9: 65.
  • Cai, Y., Zhang, J., Xiao, T., Peng, H., Sterling, S. M. et al., 2020. Distinct conformational
  • states of SARS-CoV-2 spike protein. Science, 369: 1586–1592.
  • Callaway, E., 2020. The race for coronavirus vaccines: a graphical guide. Nature, 580:-577.
  • Carvalho, T., Krammer, F. y Iwasaki, A., 2021. The first 12 months of COVID-19: a timeline
  • of immunological insights. Nature reviews. Immunology, 21: 245–256.
  • Carty, M., Guy, C. y Bowie, A. G., 2021. Detection of Viral Infections by Innate Immunity.
  • Biochemical pharmacology, 183: 114316.
  • Chavda, V. P., Vora, L. K., Pandya, A. K. y Patravale, V. B., 2021. Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management. Drug discovery today, S1359-6446:00331-7.
  • Choi, A., Koch, M., Wu, K., Chu, L., Ma, L. et al., 2021. Safety and immunogenicity of
  • SARS-CoV-2 variant RNAm vaccine boosters in healthy adults: an interim analysis. Nature medicine, 27: 2025–2031.
  • Coronaviridae Study Group of the International Committee on Taxonomy of Viruses,
  • The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature microbiology, 5:536–544.
  • Dai, L., Zheng, T., Xu, K., Han, Y. et al., 2020. A universal design of Betacoronavirus vaccines against COVID-19, MERS, and SARS. Cell, 182: 722–733.e11.
  • D’Aoust, M. A., Couture, M. M., Charland, N., Trépanier, S. et al., 2010. The production
  • of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe
  • response to pandemic influenza. Plant biotechnology journal, 8: 607–619.
  • Dey, A., Chozhavel Rajanathan, T. M., Chandra, H., Pericherla, H. et al., 2021. Immunogenic potential of ADN vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models. Vaccine, 39: 4108–4116.
  • Del Giudice, G., Rappuoli, R. y Didierlaurent, A. M., 2018. Correlates of adjuvanticity: A review on adjuvants in licensed vaccines. Seminars in immunology, 39: 14–21.
  • Di Pasquale, A., Bonanni, P., Garçon, N., Stanberry, L. R. et al., 2016. Vaccine safety evaluation: Practical aspects in assessing benefits and risks. Vaccine, 34: 6672–6680.
  • Dolgin, E. 2021. The tangled history of RNAm vaccines. Nature, 597: 318–324. Fomsgaard, A. y Liu, M. A., 2021. The key role of nucleic acid vaccines for one health. Viruses, 13: 258.
  • Formica, N., Mallory, R., Albert, G., Robinson, M. et al., 2021. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial. PLoS medicine, 18: e1003769.
  • Francica, J. R., Flynn, B. J., Foulds, K. E., Noe, A. T. et al., 2021. Vaccination with SARSCoV-2 spike protein and AS03 adjuvant induces rapid anamnestic antibodies in the lung and protects against virus challenge in nonhuman primates. bioRxiv, 2021.03.02.433390.
  • Gallardo, J., Pérez-Illana, M., Martín-González, N. y San Martín, C., 2021. Adenovirus structure: What is new? International journal of molecular sciences, 22: 5240.
  • Gao, Q., Bao, L., Mao, H., Wang, L. et al., 2020. Development of an inactivated vaccine candidate for SARS-CoV-2. Science, 369: 77–81.
  • García-Arriaza, J., Garaigorta, U., Pérez, P., Lázaro-Frías, A. et al., 2021. COVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SARSCoV-2 spike induce robust T- and B-cell immune responses and full efficacy in mice. Journal of virology, 95: e02260-20.
  • Geers, D., Shamier, M. C., Bogers, S., den Hartog, G. et al., 2021. SARS-CoV-2 variants
  • of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees. Science immunology, 6: eabj1750.
  • Gobeil, P., Pillet, S., Séguin, A., Boulay, I., Mahmood, A. et al., 2021. Interim report of a phase 2 randomized trial of a plant-produced virus-like particle vaccine for Covid-19 in healthy adults aged 18–64 and older adults aged 65 and older. medRxiv, 2021.05.14.21257248.
  • Goepfert, P. A., Fu, B., Chabanon, A. L., Bonaparte, M. I., Davis. et al., 2021. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. The Lancet. Infectious diseases, 21: 1257–1270.
  • Groenke, N., Trimpert, J., Merz, S., Conradie, A. M. et al., 2020. Mechanism of virus attenuation by codon pair deoptimization. Cell reports, 31: 107586.
  • Hobernik, D. y Bros, M., 2018. ADN vaccines-how far from clinical use? International journal of molecular sciences, 19: 3605.
  • Karikó, K., Muramatsu, H., Welsh, F.A., Ludwig, J. et al., 2008. Incorporation of pseudouridine
  • into RNAm yields superior nonimmunogenic vector with increased translational capacity and biological Stability. Molecular Therapy, 16: 1833–1840.
  • Keech, C., Albert, G., Cho, I., Robertson, A. et al., 2020. Phase 1-2 Trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. The New England journal of medicine, 383: 2320–2332.
  • Krause, P. R., Fleming, T. R., Peto, R., Longini, I. M. et al., 2021. Considerations in boosting
  • COVID-19 vaccine immune responses. Lancet, 398: 1377–1380.
  • Le Nouën, C., McCarty, T. yang, L., Brown, M. et al., 2021. Rescue of codon-pair deoptimized
  • respiratory syncytial virus by the emergence of genomes with very large internal deletions that complemented replication. Proceedings of the National Academy of Sciences of the United States of America, 118: e2020969118.
  • Lobera, J. y Cabrera, P., 2021. Evolución de la percepción social de aspectos científicos
  • de la COVID-19 (julio 2020 – enero 2021). Fundación Española para la Ciencia y la Tecnología, FECYT, 2021. E-nipo: 831210196.
  • Logunov, D. Y., Dolzhikova, I. V., Zubkova, O. V., Tukhvatulin, A. I. et al., 2020. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous primeboost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet, 396: 887–897.
  • Lundstrom, K., Barh, D., Uhal, B. D., Takayama, K. et al., 2021. COVID-19 Vaccines and thrombosis-roadblock or dead-end street? Biomolecules, 11: 1020.
  • Maginnis M. S., 2018. Virus-Receptor interactions: The key to cellular invasion. Journal of molecular biology, 430: 2590–2611.
  • Mallapaty, S., 2021: China’s COVID vaccines have been crucial — now immunity is waning. Nature, 598: 398-399.
  • Momin, T., Kansagra, K., Patel, H., Sharma, S. et al., 2021. Safety and Immunogenicity of a ADN SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India. EClinicalMedicine, 38: 101020.
  • Nooraei, S., Bahrulolum, H., Hoseini, Z. S., Katalani, C. et al., 2021. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers.
  • Journal of nanobiotechnology, 19: 59.
  • Okamura, S. y Ebina, H., 2021. Could live attenuated vaccines better control COVID-19? Vaccine, 39: 5719–5726.
  • Ong, H. K., Tan, W. S. y Ho, K. L., 2017. Virus like particles as a platform for cancer vaccine
  • development. PeerJ, 5: e4053.
  • Ortiz-Sánchez, E., Velando-Soriano, A., Pradas-Hernández, L., Vargas-Román, K. et al., 2020. Analysis of the anti-vaccine movement in social networks: A systematic review. International journal of environmental research and public health, 17: 5394.
  • Pardi, N., Hogan, M. J., Naradikian, M. S., Parkhouse, K. et al., 2018. Nucleoside-modified ARNm vaccines induce potent T follicular helper and germinal center B cell responses. The journal of experimental medicine, 215: 1571–1588.
  • Rock, K. L., Reits, E. y Neefjes, J., 2016. Present yourself! By MHC class I and MHC class
  • II Molecules. Trends in immunology, 37: 724–737.
  • Rosales-Mendoza, S., Márquez-Escobar, V. A., González-Ortega, O., Nieto-Gómez, R. y Arévalo-Villalobos, J. I., 2020. What does plant-based vaccine technology offer to the fight against COVID-19? Vaccines, 8: 183.
  • Røttingen, J. A., Gouglas, D., Feinberg, M., Plotkin, S. et al., 2017. New vaccines against
  • epidemic infectious diseases. The New England journal of medicine, 376: 610–613.
  • Rubio, P. y Carvajal, A., 2020. Coronavirus. AmbioCiencias, 18: 5-18.
  • Russell, M. W., Moldoveanu, Z., Ogra, P. L. y Mestecky, J., 2020. Mucosal immunity in COVID-19: A neglected but critical aspect of SARS-CoV-2 infection. Frontiers in immunology, 11: 611337.
  • Sadoff, J., Gray, G., Vandebosch, A., Cárdenas, V. et al., 2021. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. The New England journal of medicine, 384: 2187–2201.
  • Sahin, U., Muik, A., Derhovanessian, E., Vogler, I. et al., 2020. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature, 586: 594–599.
  • Sahin, U., Muik, A., Vogler, I., Derhovanessian, E. et al., 2021. BNT162b2 vaccine induces
  • neutralizing antibodies and poly-specific T cells in humans. Nature, 595:572–577.
  • Shiver, J. W., Fu, T. M., Chen, L., Casimiro, D. R. et al., 2002. Replication-incompetent
  • adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature, 415: 331–335.
  • Silveira, M. M., Moreira, G. y Mendonça, M., 2021. ADN vaccines against COVID-19: Perspectives and challenges. Life sciences, 267: 118919.
  • Slaoui, M. y Hepburn, M., 2020. Developing safe and effective Covid vaccines - operation
  • warp speed’s strategy and approach. The New England journal of medicine, 383: 1701–1703.
  • Spencer, A.J., Morris, S., Ulaszewska, M., Powers, C. et al., 2021. The ChAdOx1 vectored
  • vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 Beta (B.1.351) and other variants of concern in preclinical studies. bioRxiv, 2021.06.08.447308.
  • Swanson, P. A., Padilla, M., Hoyland, W., McGlinchey, K. et al., 2021. AZD1222/ChAdOx1
  • nCoV-19 vaccination induces a polyfunctional spike protein-specific Th1 response
  • with a diverse TCR repertoire. Science translational medicine, eabj7211.
  • Tang, T., Bidon, M., Jaimes, J. A., Whittaker, G. R. y Daniel, S., 2020. Coronavirus membrane
  • fusion mechanism offers a potential target for antiviral development. Antiviral research, 178: 104792.
  • Tao, K., Tzou, P. L., Nouhin, J., Gupta, R. K. et al., 2021. The biological and clinical significance
  • of emerging SARS-CoV-2 variants. Nature reviews. Genetics, 1–17.
  • Tarke, A., Sidney, J., Methot, N., Zhang, Y. et al., 2021. Negligible impact of SARS-CoV-2
  • variants on CD4 + and CD8 + T cell reactivity in COVID-19 exposed donors and vaccinees. bioRxiv, 2021.02.27.433180.
  • Tian, J. H., Patel, N., Haupt, R., Zhou, H. et al., 2021. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nature communications, 12: 372.
  • Travis C. R., 2020. As plain as the nose on your face: The case for a nasal (mucosal) route
  • of vaccine administration for Covid-19 disease prevention. Frontiers in immunology, 11: 591897.
  • Turner, J. S., O’Halloran, J. A., Kalaidina, E., Kim, W. et al., 2021. SARS-CoV-2 RNAm vaccines induce persistent human germinal centre responses. Nature, 596: 109–113.
  • Valdes-Balbin, Y., Santana-Mederos, D., Paquet, F., Fernandez, S. et al., 2021. Molecular aspects concerning the use of the SARS-CoV-2 receptor binding domain as a target for preventive vaccines. ACS central science, 7: 757–767.
  • van Doremalen, N., Lambe, T., Spencer, A., Belij-Rammerstorfer, S. et al., 2020. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature, 586: 578–582.
  • van Erp, E. A., Luytjes, W., Ferwerda, G. y van Kasteren, P. B., 2019. Fc-mediated antibody
  • effector functions during respiratory syncytial virus infection and disease. Frontiers in immunology, 10: 548.
  • Voysey, M., Clemens, S., Madhi, S. A., Weckx, L. Y. et al., 2021. Safety and efficacy of the
  • ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet, 397: 99–111.
  • Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A. et al., 2020. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 181, 281–292.e6.
  • Wang, H., Zhang, Y., Huang, B., Deng, W. et al., 2020a. Development of an inactivated
  • vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell, 182: 713–721.e9.
  • Wang, N., Shang, J., Jiang, S. y Du, L., 2020b. Subunit vaccines against emerging pathogenic human coronaviruses. Frontiers in microbiology, 11: 298.
  • Wang, Y. yang, C., Song, Y., Coleman, J. R. et al., 2021. Scalable live-attenuated SARSCoV-
  • vaccine candidate demonstrates preclinical safety and efficacy. Proceedings of the National Academy of Sciences of the United States of America, 118: e2102775118.
  • Ward, B. J., Gobeil, P., Séguin, A., Atkins, J., Boulay, I. et al., 2021. Phase 1 randomized
  • trial of a plant-derived virus-like particle vaccine for COVID-19. Nature medicine, 27: 1071–1078.
  • Woźniak, E., Tyczewska, A. y Twardowski, T., 2021. A shift towards biotechnology: Social opinion in the EU. Trends in biotechnology, 39: 214–218.
  • Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A. et al., 2020. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367: 1260–1263.
  • Wu, F., Zhao, S. yu, B., Chen, Y. M. et al., 2020. A new coronavirus associated with human respiratory disease in China. Nature, 579: 265–269.
  • Xia, S., Duan, K., Zhang, Y., Zhao, D. et al., 2020. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: Interim analysis of 2 randomized clinical trials. JAMA, 324: 951–960.
  • Yang, S., Li, Y., Dai, L., Wang, J., He, P. et al., 2021. Safety and immunogenicity of a recombinant
  • tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. The Lancet. Infectious diseases, 21: 1107–1119.
  • Zhao, X., Zheng, A., Li, D., Zhang, R. et al., 2021. Neutralization of ZF2001-elicited antisera
  • to SARS-CoV-2 variants. The Lancet. Microbe, 2: e494.
  • Zhu, N., Zhang, D., Wang, W., Li, X. et al., 2012. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunological reviews, 249: 158–175.
  • Zhu, N., Zhang, D., Wang, W., Li, X. et al., 2020a. A novel coronavirus from patients
  • with pneumonia in China, 2019. The New England journal of medicine, 382:727–733.
  • Zhu, F. C., Li, Y. H., Guan, X. H., Hou, L. H. et al., 2020b. Safety, tolerability, and immunogenicity
  • of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet, 395:1845–1854