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Vol. 25. Issue 1.
Pages 140-146 (January - March 2024)
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Vol. 25. Issue 1.
Pages 140-146 (January - March 2024)
Review article
Current situation of intranasal attenuated vaccines against respiratory syncytial virus in the child population
Situación actual de las vacunas atenuadas intranasales frente al virus respiratorio sincitial en la población infantil
Jordi Reinaa,b, Andrés Suáreza,b,*
a Unidad de Virología, Servicio de Microbiología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
b Facultad de Medicina, Universitat Illes Balears, Palma de Mallorca, Spain
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Abstract

The respiratory syncytial virus (RSV) is the cause of acute respiratory pathologies (bronchiolitis and pneumonia), which occur preferably in the paediatric population in an epidemic manner. The only way to prevent these infections is through prior vaccination >6 months. Of the different existing vaccines, attenuated vaccines, defined as those that contain an altered or modified virus to minimise its pathogenic capacity while maintaining its immunological response capacity, seem to represent an important advance. In recent years, 2 vaccine candidates based on the M2-2 gene deletion have been evaluated, those designated MEDI/ΔM2 and LID/ΔM2-2/1030s. In the study carried out in 21 seronegative children (6–24 months), they received an intranasal dose (105 PFU) of the new vaccine compared to a placebo group. 85% of those vaccinated developed a neutralising antibody titre >4 times the previous one. The combination of the Δ1313 deletion with the NS2 deletion was shown to be better for the development of an attenuated RSV recombinant vaccine candidate (ΔNS2/Δ1313), with good protective results. A new vaccine candidate designated RSV/6120/ΔNS2/1030s was developed that is identical to the previous virus RSV/ΔNS2/Δ1313/I1314L but with additional mutations. Finally, a VRS with a single replicative cycle has been developed by eliminating the gene encoding the matrix (M) protein (VRS-M-null). Most of these vaccines are still in phase 2/3 and very good results are expected.

Keywords:
Respiratory syncytial virus
Attenuated vaccines
Deletions
Resumen

El Virus Respiratorio Sincitial (VRS) es el causante de patologías respiratorias agudas (bronquiolitis y neumonías), que se presentan preferentemente en la población infantil de forma epidémica. La única forma de prevenir estas infecciones es mediante la vacunación previa de los >6 meses. De las diferentes vacunas existentes, las vacunas atenuadas, definidas como aquellas que contienen un virus alterado o modificado para disminuir al máximo su capacidad patogénica pero manteniendo su capacidad de respuesta inmunológica, parecen representar un importante avance. En los últimos años se han evaluado dos candidatas vacunales basadas en la delección de gen M2–2, las designadas como MEDI/ΔM2 y la LID/ΔM2–2/1030s. En el estudio realizado en 21 niños seronegativos (6–24 meses), éstos recibieron una dosis intranasal (105 PFU) de la nueva vacuna frente a un grupo placebo. El 85% de los vacunados desarrollaron un título de anticuerpos neutralizantes >4 veces al previo. La combinación de la delección Δ1313 con la delección de la NS2 se mostró mejor para la elaboración un candidato vacunal recombinante atenuado del VRS (ΔNS2/Δ1313), con buenos resultados protectores. Se desarrolló un nuevo candidato vacunal designado como RSV/6120/ΔNS2/1030s que es idéntico al virus previo RSV/ΔNS2/Δ1313/I1314L pero con mutaciones adicionales. Finalmente se ha desarrollado un VRS de un solo ciclo replicativo eliminando el gen codificador de la proteína de matriz (M) (VRS-M-null). La mayoría de estas vacunas están todavía en fase 2/3 y se esperan muy buenos resultados.

Palabras clave:
Virus respiratorio sincitial
Vacunas atenuadas
Delecciones genéticas

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