Viral diseases still cause major consequences to our health, society and the global economy, despite the development of a multitude of vaccines and treatments. Viruses such as the human immunodeficiency virus-1 (HIV-1), respiratory syncytial virus (RSV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause mortality and morbidity across the world. There is still much we can learn from the immune system’s response to viruses. Antibodies against viral glycoproteins are often a crucial aspect of this immune response. In the first chapters of this thesis, we focused on the role of antibodies as markers for respiratory virus infections and for population immunity screening. We investigated the functionality and breadth of antiviral antibodies to gain insight that may guide work towards improved vaccines and therapies. Moreover, we assessed the immune response to SARS-CoV-2 vaccination in vulnerable populations. Finally, we assessed experimental vaccines for SARS-CoV-2 and HIV-1 to investigate how to further steer vaccine-induced immunity. Collectively, this thesis describes novel findings on the role of polyfunctional antibodies in detecting, controlling and preventing viral infections. Increased knowledge on immunity to viruses may lead to increasingly effective antiviral strategies and reduce the burden of viral disease on human health.