In order to determine the suitability of vaccine strains established in the
1960s for a new vaccine, a comprehensive study of strain variation of aden
ovirus serotype 4 (AV 4) and AV 7 was undertaken. A 1,500-bp region of the
hexon gene containing the AV neutralization epitopes from prototype, vaccin
e, and community-acquired strains and from wild-type strains from military
personnel that cause acute respiratory disease (ARD) was sequenced and anal
yzed. The whole hexon gene from prototype strains, vaccine strains, and sel
ected isolates was sequenced. AV 7 and AV 7a were found to have distinct ge
notypes, and all vaccine and wild-type strains recovered from 1963 to 1997
had the AV 79 genotype, There was no significant strain variation in the ne
utralization epitopes of the AV 7a genotype over a 42-year period. The evol
ution of AV 4 was more complex, with continuous genetic drift punctuated by
replacement with a new strain. The current strain of AV 4, which has been
in circulation since 1995, is significantly different from the AV 4 prototy
pe and the vaccine strains. Genetic differences were confirmed to be antige
nic differences by neutralization tests, which define the new strain as an
AV 4 variant. A type-specific PCR for AV 4, AV 7/7a, and AV 21 was develope
d, and this PCR facilitated the rapid identification of isolates from outbr
eaks of ARD.