Anticuerpos neutralizantes: su rol como herramienta diagnóstica, correlato de protección y agente terapéutico en infecciones virales recientes
Neutralizing antibodies: their role as a diagnostic tool, correlate of protection, and therapeutic agent in recent viral infections

Juan Carlos Patiño-Mogrovejo, Christian Andrés Quezada-Alvear, Maybery Rosibel Suarez-Elizalde, Nereida Josefina Valero-Cedeño

Resumen


RESUMEN
Las infecciones virales continúan representando un desafío global por su capacidad de evadir la inmunidad adaptativa y generar nuevas variantes. Los anticuerpos neutralizantes (NAbs) constituyen un elemento crítico de defensa humoral, capaces de bloquear la entrada viral a la célula huésped mediante la unión específica a epítopos de proteínas estructurales, como la proteína Spike del SARS-CoV-2 o la hemaglutinina de influenza. El objetivo general de este trabajo fue analizar el papel de los NAbs como herramientas diagnósticas, correlatos de protección y agentes terapéuticos frente a infecciones virales recientes. La metodología consistió en una revisión bibliográfica actualizada de artículos científicos indexados entre 2010 y 2024, con énfasis en la evidencia experimental y clínica sobre los métodos de detección (PRNT, pVNT, sVNT) y las aplicaciones inmunológicas. Los resultados evidencian que los títulos de NAbs son indicadores fiables de inmunidad funcional, correlacionándose inversamente con el riesgo de infección sintomática. En el diagnóstico, permiten confirmar seroconversión y diferenciar fases de infección; en la clínica, orientan decisiones terapéuticas y pronósticas, incluyendo la necesidad de refuerzos vacunales o la administración de anticuerpos monoclonales. Asimismo, la ingeniería de anticuerpos ha desarrollado versiones bi-específicas y con vida media prolongada, mejorando su eficacia frente a variantes virales. Los NAbs representan un biomarcador integral con relevancia diagnóstica, terapéutica y epidemiológica. Su estandarización internacional y accesibilidad equitativa son esenciales para fortalecer la inmunovigilancia global y garantizar un uso ético de las terapias de última generación.

ABSTRACT
Viral infections continue to represent a global challenge due to their ability to evade adaptive immunity and generate new variants. Neutralizing antibodies (NAbs) constitute a critical component of the humoral defense, capable of blocking viral entry into the host cell through specific binding to structural protein epitopes, such as the SARS-CoV-2 Spike protein or the influenza hemagglutinin. The main objective of this work was to analyze the role of NAbs as diagnostic tools, correlates of protection, and therapeutic agents against recent viral infections. The methodology consisted of an updated bibliographic review of scientific articles indexed between 2010 and 2024, emphasizing experimental and clinical evidence on detection methods (PRNT, pVNT, sVNT) and immunological applications. The results show that NAb titers are reliable indicators of functional immunity, correlating inversely with the risk of symptomatic infection. In diagnostics, they allow confirmation of seroconversion and differentiation of infection stages; in clinical practice, they guide therapeutic and prognostic decisions, including the need for vaccine boosters or monoclonal antibody administration. Moreover, antibody engineering has developed bispecific and extended half-life versions, improving their efficacy against viral variants. NAbs represent an integrated biomarker with diagnostic, therapeutic, and epidemiological relevance. Their international standardization and equitable accessibility are essential to strengthen global immunosurveillance and ensure the ethical use of next-generation therapies.

Recibido: 05-11-2025
Aceptado: 12-12-2025
Publicado: 02-02-2026


Palabras clave


anticuerpos monoclonales; anticuerpos neutralizantes; pruebas serológicas; enfermedades virales; inmunidad humoral. monoclonal antibodies; neutralizing antibodies; serological tests; viral diseases; humoral immunity.

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Referencias


Amanat, F., & Krammer, F. (2020). SARS-CoV-2 vaccines: Status report. Immunity, 52(4), 583–589. https://doi.org/10.1016/j.immuni.2020.03.007

Berneck, B. S., Rockstroh, A., Fertey, J., Grunwald, T., & Ulbert, S. (2020). A recombinant Zika virus envelope protein with mutations in the conserved fusion loop leads to reduced antibody cross-reactivity upon vaccination. Vaccines, 8(4), 603. https://doi.org/10.3390/vaccines8040603

Burton, D. R. (2023). Antiviral neutralizing antibodies: from in vitro to in vivo activity. Nature Reviews. Immunology, 23(11), 720–734. https://doi.org/10.1038/s41577-023-00858-w

Cai, Z., Kalkeri, R., Zhu, M., Cloney-Clark, S., Haner, B., Wang, M., Osman, B., Dent, D., Feng, S. L., Longacre, Z., Glenn, G., & Plested, J. S. (2024). A Pseudovirus-Based Neutralization Assay for SARS-CoV-2 Variants: A Rapid, Cost-Effective, BSL-2-Based High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation. Microorganisms, 12(3), 501. https://doi.org/10.3390/microorganisms12030501

Corti, D., Purcell, L. A., Snell, G., & Veesler, D. (2021). Tackling COVID-19 with neutralizing monoclonal antibodies. Cell, 184(12), 3086–3108. https://doi.org/10.1016/j.cell.2021.05.005

Earle, K. A., Ambrosino, D. M., Fiore-Gartland, A., Goldblatt, D., Siber, G. R., Dull, P., & Plotkin, S. A. (2021). Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine, 39(32), 4423–4428. https://doi.org/10.1016/j.vaccine.2021.05.063

García-Beltrán, W. F., Lam, E. C., St Denis, K., Nitido, A. D., Garcia, Z. H., Hauser, B. M., ... & Balazs, A. B. (2021). Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell, 184(9), 2372–2383.e9. https://doi.org/10.1016/j.cell.2021.03.013

Gruell, H., Vanshylla, K., Weber, T., Barnes, C. O., Kreer, C., & Klein, F. (2022). Antibody-mediated neutralization of SARS-CoV-2. Immunity, 55(6), 925–944. https://doi.org/10.1016/j.immuni.2022.05.005

Halstead, S. B. (2003). Neutralization and antibody-dependent enhancement of dengue viruses. Advances in Virus Research, 60, 421–467. https://doi.org/10.1016/s0065-3527(03)60007-x

Haynes, B. F., & Burton, D. R. (2017). Developing broadly neutralizing antibodies for HIV-1 prevention. New England Journal of Medicine, 377(3), 211–213. https://doi.org/10.1056/NEJMp1705353

Karki, R., Sharma, B. R., Tuladhar, S., Williams, E. P., Zalduondo, L., Samir, P., Zhen, M., Sundaram, B., Banoth, B., Malireddi, R., Schreiner, P., Neale, G., Vogel, P., Webby, R., Jonsson, C., & Kanneganti, T. D. (2021). Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell, 184(1), 149–168.e17. https://doi.org/10.1016/j.cell.2020.11.025

Khoury, D. S., Cromer, D., Reynaldi, A., Schlub, T. E., Wheatley, A. K., Juno, Subbarao, K., Kent, S., Triccas, J., & Davenport, M. P. (2021). Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nature Medicine, 27(7), 1205–1211. https://doi.org/10.1038/s41591-021-01377-8

Klasse, P. J. (2014). Neutralization of virus infectivity by antibodies: Old problems in new perspectives. Advances in Biology, 2014, 157895. https://doi.org/10.1155/2014/157895

Krammer, F., & Simon, V. (2020). Serology assays to manage COVID-19. Science (New York, N.Y.), 368(6495), 1060–1061. https://doi.org/10.1126/science.abc1227

Liu, L., Suscovich, T. J., Fortune, S. M., & Alter, G. (2018). Beyond binding: antibody effector functions in infectious diseases. Nature Reviews. Immunology, 18(1), 46–61. https://doi.org/10.1038/nri.2017.106

Liu, M., Gan, H., Liang, Z., Liu, L., Liu, Q., Mai, Y., Chen, H., Lei, B., Yu, S., Chen, H., Zheng, P., & Sun, B. (2023). Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies. Frontiers in microbiology, 14, 1122868. https://doi.org/10.3389/fmicb.2023.1122868

Marston, H. D., Paules, C. I., & Fauci, A. S. (2018). Monoclonal Antibodies for Emerging Infectious Diseases - Borrowing from History. The New England Journal of Medicine, 378(16), 1469–1472. https://doi.org/10.1056/NEJMp1802256

Morens, D. M., & Fauci, A. S. (2020). Emerging pandemic diseases: How we got to COVID-19. Cell, 182(5), 1077–1092. https://doi.org/10.1016/j.cell.2020.08.021

Peissert, F., Pedotti, M., Corbellari, R., Simonelli, L., De Gasparo, R., Tamagnini, E., Plüss, L., Elsayed, A., Matasci, M., De Luca, R., Cassaniti, I., Sammartino, J., Piralla, A., Baldanti, F., Neri, D., & Varani, L. (2023). Adapting Neutralizing Antibodies to Viral Variants by Structure-Guided Affinity Maturation Using Phage Display Technology. Global challenges (Hoboken, NJ), 7(10), 2300088. https://doi.org/10.1002/gch2.202300088

Planas, D., Saunders, N., Maes, P., Guivel-Benhassine, F., Planchais, C., Buchrieser, J., Bolland, W., Porrot, F, Staropoli, I., Lemoine, F., Péré, H., Veyer, D., Puech, J., Rodary, J., Baele, G., Dellicour, S., Raymenants, J., Gorissen, S., Geenen, C… Schwartz, O. (2022). Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature, 602(7898), 671–675. https://doi.org/10.1038/s41586-021-04389-z

Plotkin, S. A. (2010). Correlates of protection induced by vaccination. Clinical and Vaccine Immunology: CVI, 17(7), 1055–1065. https://doi.org/10.1128/CVI.00131-10

Santeliz J. (2022). El pecado antigénico original: un desafío para el diseño de nuevas vacunas contra el SARS-CoV-2? Boletín Médico de Postgrado, 38(2), 6-7. DOI: 10.5281/zenodo.6809253 ISSN: 2791-3848

Sarker, A., Dhama, N., & Gupta, R. D. (2023). Dengue virus neutralizing antibody: a review of targets, cross-reactivity, and antibody-dependent enhancement. Frontiers in immunology, 14, 1200195. https://doi.org/10.3389/fimmu.2023.1200195

Sette, A., & Crotty, S. (2021). Adaptive immunity to SARS-CoV-2 and COVID-19. Cell, 184(4), 861–880. https://doi.org/10.1016/j.cell.2021.01.007

Stephenson, K. E., Wagh, K., Korber, B., & Barouch, D. H. (2020). Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention. Annual review of immunology, 38, 673–703. https://doi.org/10.1146/annurev-immunol-080219-023629

Taubenberger, J. K., & Morens, D. M. (2008). The pathology of influenza virus infections. Annual Review of Pathology: Mechanisms of Disease, 3, 499–522. https://doi.org/10.1146/annurev.pathmechdis.3.121806.154316

Tan, C. W., Chia, W. N., Qin, X., Liu, P., Chen, M. I., Tiu, C., Hu, Z., Chen, V., Young, B., Sia, W., Tan, Y., Foo, R., Yi Y., Lye, D., Anderson, D., & Wang, L. F. (2020). A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Nature Biotechnology, 38(9), 1073–1078. https://doi.org/10.1038/s41587-020-0631-z

Van Gils, M. J., van den Blink, A. G., & Goudsmit, J. (2022). Using neutralizing antibody levels to guide clinical decisions for COVID-19. Nature Reviews Immunology, 22(5), 269–270. https://doi.org/10.1038/s41577-022-00713-3

Vatti, A., Monsalve, D. M., Pacheco, Y., Chang, C., Anaya, J. M., & Gershwin, M. E. (2017). Original antigenic sin: A comprehensive review. Journal of autoimmunity, 83, 12–21. https://doi.org/10.1016/j.jaut.2017.04.008

Wang, Z., Lorenzi, J. C. C., Muecksch, F., Finkin, S., Viant, C., Gaebler, C., Cipolla, M., Hoffmann, H., Oliveira, T., Oren, D., Ramos, V., Nogueira, L., Michailidis, E., Robbiani, D., Gazumyan, A., Rice, C., Hatziioannou, T., Bieniasz, P… Nussenzweig, M. C. (2021). Enhanced SARS-CoV-2 neutralization by dimeric IgA. Science Translational Medicine, 13(577), eabf1555. https://doi.org/10.1126/scitranslmed.abf1555

Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T., Vollmar, P., Rothe, C., Hoelscher, M., Bleicker, T., Brünink, S., Schneider, J., Ehmann, R., Zwirglmaier, K., Drosten, C., & Wendtner, C. (2020). Virological assessment of hospitalized patients with COVID-2019. Nature, 581(7809), 465–469. https://doi.org/10.1038/s41586-020-2196-x

World Health Organization. (2021). Neutralizing antibody assays for SARS-CoV-2: Technical brief. World Health Organization. https://www.who.int/publications/i/item/WHO-2019-nCoV-Seroepidemiology-Assays-2021.1

Zhu, F., Althaus, T., Tan, C. W., Costantini, A., Chia, W. N., Van Vinh Chau, N., Tan, L., Mattiuzzo, G., Rose, N., Voiglio, E., & Wang, L. F. (2022). WHO international standard for SARS-CoV-2 antibodies to determine markers of protection. The Lancet. Microbe, 3(2), e81–e82. https://doi.org/10.1016/S2666-5247(21)00307-4


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