The Repeated Setbacks of HIV Vaccine Development Laid the Groundwork for SARS-CoV-2 Vaccines

National Bureau of Economic Research Working Paper 28587

The decades-long effort to produce a workable HIV vaccine has hardly been a waste of public and private resources. To the contrary, the scientific know-how acquired along the way has served as the critical foundation for the development of vaccines against the novel, pandemic SARS-CoV-2 virus. We retell the real-world story of HIV vaccine research – with all its false leads and missteps – in a way that sheds light on the current state of the art of antiviral vaccines. We find that HIV-related R&D had more than a general spillover effect. In fact, the repeated failures of HIV vaccine trials have served as a critical stimulus to the development of successful vaccine technologies today. We rebut the counterargument that HIV vaccine development has been no more than a blind alley, and that recently developed vaccines against COVID-19 are really descendants of successful vaccines against Ebola, MERS, SARS-CoV-1 and human papillomavirus. These successful vaccines likewise owe much to the vicissitudes of HIV vaccine development.

The SARS-CoV-1 outbreak in 2002-2003 and the continuing reintroduction of MERS-CoV on the Arabian Peninsula a decade later sent a clear message to the public health and scientific communities well before the December 2019 outbreak of SARS-CoV-2 in Wuhan, China. At any minute, a novel, lethal respiratory coronavirus could emerge with the potential for pandemic human-to-human spread. Piggybacking on the major advances in virology, immunology and molecular biology achieved during the scientific confrontation with HIV, researchers already knew that human coronaviruses were positive-sense RNA viruses with a key spike glycoprotein that protruded from viral envelope. They already knew that the spike glycoprotein could bind to viral receptors on host target cells. The spike glycoprotein of SARS-Cov-1, they knew as well, could bind a receptor called ACE2 in human lungs. They knew it was coming and, at least from the scientific point of view of vaccine development, they were ready.

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