During 17 years (until 1985) he pursued an academic career at the Venezuelan Institute for Scientific Research (IVIC), attaining positions as full professor of virology and chairman of its Department of Microbiology and Cell Biology.
During his undergraduate teenage years, Esparza teamed up with some of his teachers in viral research studies designed to characterize a large zoonotic outbreak of Venezuelan equine encephalitis affecting people and riding beasts in the nearby Guajira region and its surroundings.
As part of a sabbatical leave Esparza was invited by the Department of Microbiology & Immunology at Duke University (Durham, N.C.) to work with Wolfgang Joklik.
He also applied such tools to the study of rotaviruses, a leading worldwide cause of infantile diarrhea which severely affects and causes many deaths in toddlers living in developing countries like Venezuela.
In 1988 Esparza joined the recently created WHO Global Programme on AIDS and in 1996 he was required to head the Vaccine Development Unit sponsored jointly by WHO-UNAIDS, a task he undertook until 2004.