RESUMEN
Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Femenino , Masculino , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Inmunogenicidad Vacunal , Adulto Joven , Eficacia de las Vacunas , Vietnam , Adolescente , Vacunas de ARNm , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/administración & dosificaciónRESUMEN
Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inborn error of metabolism affecting isoleucine catabolism and ketone body utilization. This disorder is clinically characterized by intermittent ketoacidotic episodes with no clinical symptoms between episodes. In general, T2 gene mutations are heterogeneous. No common mutations have been identified and more than 70 mutations have been identified in 70 patients with T2 deficiency (including unpublished data). We herein identified a common mutation, R208X, in Vietnamese patients. We identified R208X homozygously in six patients and heterozygously in two patients among eight Vietnamese patients. This R208X mutation was also identified heterozygously in two Dutch patients, however, R208X mutant alleles in the Vietnamese have a different haplotype from that in the Dutch, when analyzed using Msp I and Taq I polymorphisms in the T2 gene. The R208X mutant allele was not so frequent in the Vietnamese since we could not find that mutant allele in 400 healthy Vietnamese controls using the Nla III restriction enzyme assay. DNA diagnosis of T2 deficiency may be applicable to the Vietnamese population.