Multivalent nanoparticle vaccine candidates against sarbecoviruses and HIV-1

Sarbecoviruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus 1 (HIV-1) continue to pose substantial threats to global public health and economic stability. Developing effective vaccines against these viruses is a critical step toward mitigating their spread and impact. This thesis explores various design strategies to develop such vaccines, focusing on inducing potent and broadly neutralizing antibody (NAb) responses. The initial sections discuss the development and evaluation of vaccines against SARS-CoV-2 and other sarbecoviruses, and demonstrate that effective vaccines can be developed with only minor modifications to the spike protein (S) antigen. Furthermore, multivalent vaccines incorporating S antigens from multiple sarbecovirus strains were shown to elicit broad NAb responses. In contrast, developing vaccines against HIV-1 presented more complex challenges. The HIV-1 envelope protein (Env) antigen requires extensive modifications to be effectively presented in a vaccine, yet its antigenicity remains relatively low. The antigenicity of the Env antigen can be enhanced through multimerization on nanoparticles (NPs). However, even with this approach, multivalent NP vaccines against HIV-1 were shown to induce only minimal NAb responses, which lacked sufficient breadth. These findings highlight that vaccine design presents unique challenges based on the specific pathogen being targeted. The distinct properties of each pathogen play a critical role in shaping the vaccine development strategy.