Why is proof of past DENV infection required before vaccination?

Administration of Dengvaxia to a person who has never been infected with DENV may result in an increased risk of hospitalization and severe dengue illness if they are infected with natural (wild type) DENV for the first time after vaccination. Multiple complex mechanisms likely contribute to increased disease severity during a second DENV infection. The published ACIP recommendation provides a detailed description of these mechanisms at www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-H.pdf. In addition, CDC has developed simple illustrations and descriptions to explain this phenomenon at https://www.cdc.gov/dengue/hcp/vaccine/eligibility.html.

In a person who has never been infected with DENV, vaccination with Dengvaxia may “stand in” (immunologically) for the first natural infection, resulting in an increased risk of severe dengue in response to the first natural infection because the immune system responds as if that infection were the “second” infection.