Vaccines that elicit a protective broadly neutralizing antibody (bNAb) response and monoclonal
antibody therapies are critical for the treatment and prevention of viral infections. However, isolation
of protective neutralizing antibodies has been challenging for some viruses, notably those with
high antigenic diversity or those that do not elicit a bNAb response in the course of natural infection.
Here, we discuss recent work that employs protein engineering strategies to design immunogens
that elicit bNAbs or engineer novel bNAbs. We highlight the use of rational, computational, and
combinatorial strategies and assess the potential of these approaches for the development of new
vaccines and immunotherapeutics.