Live Attenuated Influenza A Virus Vaccines in Children: Results of a Field Trial

One hundred three young children were inoculated intranasally with either influenza AI California/10/78 cold-recombinant vaccine (106. 1 500/0 tissue culture infective doses [TCIDsol per child), CR-37 (HINI), or influenza A/Washington/897/80 cold-recom-binant vaccine (106.s TCIDsoper child), CRA8 (H3N2). The vaccine was well tolerated. Of the 51 children vaccinated with CR-37 (HINI), 45 were initially seronegative for this virus; 33 of the 45 became infected with the vaccine virus, as indicated by a fourfold rise in antibody titer or by shedding of vaccine virus. Of the 52 children vaccinated with CR-48 (H3N2), six were initially seronegative and all were infected; 46 were initially seropositive and 25 of these children developed fourfold rises in antibody titer. An out-break of influenza A (H3N2 type predominated) occurred in Huntington one to three months after the children were vaccinated. Significantly fewer febrile illnesses occurred in the CR-48 (H3N2) vaccine group than among the CR-37 (HIN1) vaccine group. Hemagglutination inhibition antibody (titer, ~I:32) to H3N2 was significantly associ-ated with protection from illness and infection with influenza A/H3N2. Cold-recombinant influenza A viruses have been evaluated previously in several clinical trials for their potential as live attenuated vaccines [1-7]. Recent cold-recombinant influenza vaccines have been genotyped and found to consist of reas-sortants containing novel "donor " hemagglutinin and neuraminidase genes with the six genes that code for the internal proteins derived from the parent cold-adapted virus, influenza AIAnn Ar-bor /6/60 [8]. Reassortant viruses with six genes from the cold-adapted parent exhibit genetic stability after prolonged replication in children; Received for publication April 16, 1984, and in revised for