IMMUNIZATION WITH INACTIVATED MEASLES VIRUS VACCINE: EFFECT OF BOOSTER DOSE AND RESPONSE TO NATURAL CHALLENGE

Abstract

A group of 40 kindergarten and first-grade school children were immunized with three doses of inactivated measles virus vaccine, or an equivalent placebo, at 0, 1, and 4 weeks as part of a larger controlled field trial. A booster dose of vaccine was administered at 8 months. A sharp outbreak of measles challenged the study group at 21 months. The serological response was followed by measuring neutralizing hemagglutination-inhibiting, and complement-fixing antibodies. Following challenge with wild measles virus, the serological and clinical evidences of viral replication were documented. After three doses of inactivated measles vaccine, 11 seronegative children developed antibody, as measured by all three serologic techniques. The titers were approximately one-half to one-third those observed after natural infection. By 8 months, antibody had fallen to low or non-measurable levels. A booster dose at this time gave rise to an accelerated or secondary-type response, and resulted in titers which averaged twofold higher than the primary response. Following the booster dose the titers appeared to fall more slowly, and at 21 months following the primary series, all children retained significant levels. Of 12 seronegative children receiving placebo, challenge with natural measles infection at 21 months resulted in 11 cases of regular measles and 1 case of mild measles. Of the 11 seronegative children receiving vaccine, 7 developed a highly atypical illness, and 4 suffered no illness. The atypical illness was characterized by minimal respiratory complaints and a sparse rash. Ten of the vaccinated group demonstrated unequivocal serological evidence of measles viral replication; the eleventh who had no known exposure to measles showed no antibody rise and may have had an unrelated exanthematous infection. It was shown that measles virus infection can occur in the presence of a modest to high circulating antibody titer which had been induced by immunization with inactivated vaccine. Evidence was reviewed which indicates that antibody resulting from inactivated measles vaccine may be qualitatively different from that produced following natural infection.