RESUMO
Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Sítios de Ligação/genética , COVID-19/metabolismo , COVID-19/prevenção & controle , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Mapeamento de Epitopos , Epitopos/química , Epitopos/imunologia , Epitopos/metabolismo , Humanos , Camundongos Transgênicos , Testes de Neutralização , Ligação Proteica , Conformação Proteica , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Análise de SobrevidaRESUMO
Current consumer preferences for both clean label food ingredients and convenience-based foods has provided a unique opportunity to explore the application of novel natural food preservatives in sous vide products. The anaerobic environment and relatively low thermal processing of the sous vide process creates a favorable environment for the survival, germination, and outgrowth of spore-forming bacterium Clostridium perfringens. The aim of this study was to identify effective novel natural ingredient formulations against C. perfringens and apply them within a vacuum-sealed sous vide chicken model exposed to abusive storage and chilling conditions. Among six commercial vinegar-based formulations, liquid vinegar with citrus extract (CE; 1.0%) and with lemon juice concentrate (LJC; 1.5%) were identified as the most effective at inhibiting three individual C. perfringens strains. Both reduced viable cell counts by 5 log CFU/mL (P < 0.05), whereas reductions in spore counts ranged from 2 to 4 log CFU/mL depending on formulation and concentration used. Once incorporated to chicken meat 1.0% CE and 1.5% LJC before sous-vide cooking, completely inhibited the growth of mixed C. perfringens strains (P < 0.05) during storage for 16 days at 12 and 16 °C. Exponential cooling from 54 to 4 °C was performed for 18 h to imitate abusive storage conditions. CE and LJC at 3.0% inhibited growth and reduced counts by 3.4 and 2.9 log CFU/g compared to respective controls. Treatments CE and LJC could be implemented within the formulation of a sous vide chicken product to provide an effective protection against C. perfringens meeting clean label expectations.