<p dir="ltr">Emerging infectious diseases like severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and human immunodeficiency virus-1 (HIV-1) infections have caused global pandemics, underscoring the need for effective vaccines. To date, breakthrough SARS-CoV-2 infections and HIV-1 vaccine failures highlight the importance for a deeper understanding of vaccine-induced immune responses necessary for protection against natural escape variants with implications on viral transmissibility and antigen immunogenicity. In this study, I aim to address the critical issues of vaccine efficacy against variants of concern (VOCs) of SARS-CoV-2 and a clinical trial of a novel therapeutic vaccine to potentiate host immunity against HIV-1. I hypothesized that different vaccines may display different immunogenicity and durability against viral infection, which is important in determining their clinical applications.</p><p dir="ltr">My data aimed to:</p><p dir="ltr">1. Address critical issues related to approved vaccine efficacy against SARS-CoV-2 VOCs in the real world;</p><p dir="ltr">2. Investigate the impact of naturally occurring spike mutations on VOC infectivity and immunogenicity; and</p><p dir="ltr">3. Assess the safety and immunogenicity of a novel PD-1-based therapeutic HIV vaccine in individuals living with HIV-1 with stable ART.</p>