Cold-Recombinant Influenza A/California/10/78 (H1N1) Virus Vaccine (CR-37) in Seronegative Children: Infectivity and Efficacy Against Investigational Challenge

Forty-seven seronegative children were inoculated intranasally with influenza A/California/10/78 (HINl) cold-recombinant vaccine (CR-37). Doses ranged from 103.2 to 107.2 TCID50 per child. The dose necessary to infect 50% of children (one HID50) was ∼103.5 TCID50. Only two of eight children given 103.2 TCID50 became infected, and neither shed virus. The majority of children who were given 104.2, 105.2, 106.2, or 107.2 TCID50 of CR-37 became infected. Twenty-four of 39 children given greater than one HID50 of CR-37 shed vaccine virus. Overall, 31 of 39 became infected, as indicated by shedding of virus or antibody response or both. Although virus was shed for up to 12 days postinoculation, shedding of revertant virus was not detected. Six months after primary vaccination 26 children were challenged intranasally with 106.2 TCID50 of CR-37. Of 21 children previously infected with CR-37, only eight had further antibody increase, and none shed vaccine virus. In contrast, five of five (P < .05) children not infected with CR-37 at the time of initial inoculation were infected with the challenge inoculum (as indicated by a fourfold rise in antibody titer) and three of five children shed vaccine virus. Previous infection with CR-37 conferred significant protection from challenge with a high dose of CR-37.