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1.
J Infect Dis ; 225(1): 34-41, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34758086

RESUMEN

BACKGROUND: Vaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission around the world. METHODS: In this study, we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model. RESULTS: Hamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity. CONCLUSIONS: Overall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease.


Asunto(s)
Vacunas contra el Adenovirus/administración & dosificación , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Mesocricetus , Vacunas contra el Adenovirus/inmunología , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Cricetinae , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunación
2.
Antimicrob Agents Chemother ; 65(8): e0048621, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34060895

RESUMEN

Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacterales by combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution. For 64 clinical isolates tested, the MIC50 and MIC90 values of aztreonam-avibactam were 0.5/4 µg/ml and 8/4 µg/ml, respectively. Aztreonam-avibactam displayed potent in vitro activity against the MBL-producing Enterobacterales tested.


Asunto(s)
Aztreonam , beta-Lactamasas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/farmacología , Aztreonam/farmacología , Ceftazidima , Combinación de Medicamentos , Farmacorresistencia Microbiana , Humanos , Laboratorios , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genética
3.
Sci Transl Med ; 14(658): eabn6868, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35511920

RESUMEN

Transmission-blocking strategies that slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect against coronavirus disease 2019 (COVID-19) are needed. We have developed an orally delivered adenovirus type 5-vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here, we demonstrated that hamsters vaccinated by the oral or intranasal route had robust and cross-reactive antibody responses. We then induced a postvaccination infection by inoculating vaccinated hamsters with SARS-CoV-2. Orally or intranasally vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters after SARS-CoV-2 challenge. Naïve hamsters exposed in a unidirectional air flow chamber to mucosally vaccinated, SARS-CoV-2-infected hamsters also had lower nasal swab viral RNA and exhibited fewer clinical symptoms than control animals, suggesting that the mucosal route reduced viral transmission. The same platform encoding the SARS-CoV-2 spike and nucleocapsid proteins elicited mucosal cross-reactive SARS-CoV-2-specific IgA responses in a phase 1 clinical trial (NCT04563702). Our data demonstrate that mucosal immunization is a viable strategy to decrease SARS-CoV-2 disease and airborne transmission.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adenoviridae , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Ensayos Clínicos Fase I como Asunto , Cricetinae , Humanos , ARN Viral , SARS-CoV-2 , Índice de Severidad de la Enfermedad
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