Historical Advances in Structural and Molecular Biology and How They Impacted Vaccine Development

Reverse Vaccinology 2.0 [Display omitted] •The development of vaccines until the mid-20th century was based on killed organisms or organisms passaged to reduce virulence.•In the last 70 years, cell culture and molecular biology have enabled the use of specific mutations to attenuate organisms and the use of specific proteins to induce protection.•The pace of vaccine development is now much faster than ever before. Vaccines are among the greatest tools for prevention and control of disease. They have eliminated smallpox from the planet, decreased morbidity and mortality for major infectious diseases like polio, measles, mumps, and rubella, significantly blunted the impact of the COVID-19 pandemic, and prevented viral induced cancers such as cervical cancer caused by human papillomavirus. Recent technological advances, in genomics, structural biology, and human immunology have transformed vaccine development, enabling new technologies such as mRNA vaccines to greatly accelerate development of new and improved vaccines. In this review, we briefly highlight the history of vaccine development, and provide examples of where advances in genomics and structural biology, paved the way for development of vaccines for bacterial and viral diseases.