Abstract
In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8 + T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.
Keywords: SARS- CoV-2; U-Omp19; adjuvant; germinal center cells; protease inhibitor.
【저자키워드】 Protease inhibitor, SARS- CoV-2, adjuvant, U-Omp19, germinal center cells, 【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, coronavirus, T-cell Response, Th1, variant, adjuvants, virus, CD8, Receptor binding domain, Antigen, B cell, Formulation, Protease inhibitor, RBD, plasmablasts, Lungs, SARS- CoV-2, Alpha, K18-hACE2 mice, Germinal center, adjuvant, respiratory, intranasal, spleen, T-cell responses, mucosal, Combination, Frequency, neutralization capacity, alum, acute respiratory syndrome, acute respiratory syndrome coronavirus, clinical development, significantly increased, Result, composed, addition, evaluated, the vaccine, Brucella, 【제목키워드】 COVID-19, SARS-CoV-2, protection, novel, center, Specific, increase, Against, Containing, Germinal,