Antiviral monoclonal antibodies inform vaccine design

HIV-1 vaccine research has made significant progress since the start of the HIV-1 pandemic in the early 1980’s. A deeper understanding of the Envelope glycoprotein (Env) immunogen has resulted in, what seem to be, increasingly better immune responses after vaccination. Nevertheless, the desired broadly neutralizing response needed for sufficient protection from viral infection has not yet been achieved. Characterization of the immune responses after immunization with improved Env vaccine candidates becomes ever more important to determine the caveats of these current Env designs. In this thesis antibody responses are characterized after animal immunizations with various Env protein designs. Certain features of Env immunogens, like possessing large glycan holes and/or the presence of an exposed base, are shown to be very immunodominant. Large proportions of the antibody responses detailed in this thesis are directed to these sites. Nonetheless, very potent antibodies or antibodies with limited breadth were also found and described. Teaching us that specific epitopes on Env immunogens might have the potential to develop into a broader response, provided the immune response is guided in the correct direction by specifically designed immunogens and more complex immunization schemes. Combined this information helps to shape the next generation of Env vaccine designs. Designs that hopefully induce a sufficiently broad and potent response to prevent HIV-1 infection. Lastly, as shown by the characterization of antibodies from SARS-COV2 infected individuals, the methods described in this thesis can be easily translated to other viruses and species.