Anatomy of a trial: a historical view of the Monroe inactivated hepatitis A protective efficacy trial

Interference of Antibody Production to Hepatitis B Surface Antigen in a Combination Hepatitis A/Hepatitis B Vaccine

“…studies of the Merck hepatitis A vaccine (VAQTA) have evaluated the safety and immunogenicity of doses ranging from 6 to 50 U in healthy individuals [1][2][3][4].…”

Concomitant administration of hepatitis A vaccine with measles/mumps/rubella/varicella and pneumococcal vaccines in healthy 12- to 23-month-old children

“…1, [3][4][5][6][7] ProQuad™ [measles, mumps, rubella and varicella vaccine live (MMRV vaccine); Merck Sharp and Dohme Corp. ] …”

The History of Hepatitis A

“…Meanwhile and serendipitously during these preparations, the CDC was informed of a hepatitis A outbreak in an orthodox Jewish community in Monroe in Upstate New York. The high attack rate of HAV in this town and the relative self-seclusion of its residents enabled the design of a clinical efficacy trial by David Nalin, Alan Werzberger, Daniel Shouval, and coworkers 30,31 with a much smaller sample size than in the Thai study. At the beginning of an outbreak, 1037 healthy seronegative children (2-16 years) were randomized to receive a single intramuscular injection of the formalin-inactivated HAV vaccine or placebo.…”

“…24 During the last four decades, significant progress has been achieved in understanding the genomic organization, molecular epidemiology, diagnosis, [25][26][27][28][29] and prevention of HAV infection. 15,[30][31][32][33] Formaldehyde-inactivated hepatitis A vaccines were already licensed in 1991 and 1995 in Europe and the United States, respectively, 31,32 whereas a live attenuated HAV vaccine has been available in China since 1992. 34 To date, it can be stated without reservation that similar to hepatitis B, hepatitis A is a vaccine-preventable disease, as originally assessed following the hepatitis virus transmission studies by the late Saul Krugman.…”