Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children.
J Infect Dis
; 221(4): 534-543, 2020 02 03.
Article
em En
| MEDLINE
| ID: mdl-31758177
ABSTRACT
BACKGROUND:
The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children.METHODS:
Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.RESULTS:
Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.CONCLUSIONS:
LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
RNA Polimerase Dependente de RNA
/
Vacinação
/
Deleção de Genes
/
Vírus Sincicial Respiratório Humano
/
Infecções por Vírus Respiratório Sincicial
/
Vacinas contra Vírus Sincicial Respiratório
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos