Guided by glycoproteins Insights from antibody responses enable viral vaccine design

Viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the human immunodeficiency virus 1 (HIV-1) pose ongoing global health challenges, with significant implications for public health and economic stability. To effectively combat these viruses, it is crucial to investigate their properties, with the ultimate goal of developing antiviral drugs and preventive vaccines. Central to this this thesis is the exploration of the relationship between the immune system's production of antibodies and viral glycoproteins that facilitate viral infection. Studying the immune response to a particular virus or vaccine can help identify vulnerable sites on viral glycoproteins. Understanding the molecular mechanisms underlying this exact recognition can then serve as a basis for new vaccine candidates aimed at eliciting similar responses. The first part of this thesis identified vulnerable regions on SARS-CoV-2 spike (S) protein, offering rapid therapeutic potential as well as tools to study the novel coronavirus S protein. We contribute to knowledge of how the immune system responds to SARS-CoV-2, exposing vulnerabilities on the S protein and offering insights into the mechanisms by which vaccines can induce a potent NAb response. In the second part, we utilize vulnerabilities on HIV-1 envelope (Env) to design a vaccine that can induce antibodies against one of the few vulnerable regions of HIV-1 Env. Collectively, this thesis explores the interconnected nature of antibodies and viral glycoproteins, highlighting the crucial role of antibodies in the fight against viral infections and the importance of innovative vaccine development strategies.