One of the major goals of the USPHS is the regional elimination of measles by the year 2000, a goal that is achievable due to an increase in immunization rates and implementation of a two dose schedule for measles vaccine. However, there are still some unanswered questions regarding optimal use of measles vaccines . For example, research is needed in order to understand the safest method for immunization of immunocompomised children, such as those with HIV infection, who could suffer serious disease as the result of measles infection or serve as a focus of persistent shedding and spread of measles virus that could impede eradication efforts. In addition, increasing numbers of infants are born to mothers with vaccine induced immunity. These mothers have lower levels of measles antibody than mothers with immunity induced by wild type measles infection. As a result, infants born to vaccinated mothers have lower levels of passively acquired antibody at birth and these infants become susceptible to measles infection early, with loss of antibody by 6-9 months of age. Previously, vaccine failure in infants less than 12 months of age was thought to result from neutralization of vaccine virus with passively acquired antibody. It is not known if immunization of young infants with or without passive antibody would prime for measles specific cell mediated immune responses, or if immaturity of the infant immune system contributes to vaccine failure. Dr. Hayley Gans, along with Drs. Maldonado, DeHovitz and Arvin at Stanford Unversity Medical Center, evaluated and compared T cell and B cell responses to immunization with live attenuated measles or mump virus vaccine at 6, 9 or 12 months of age. Interestingly, B cell responses to measles or mumps were diminished in the presence of passively acquired maternal antibody as expected, but also appeared to be age dependent as the lowest geometric mean titers were observed in infants immunized at 6 months even if they lacked passive antibody at the time of immunization. In contrast, vaccine specific T-cell priming occurred in each age group and was not inhibited by the presence of maternal antibody. These results indicated that measles immunization of young infants may be of benefit and efficacy of infant immunization deserves further study. Dr. Charles Lebaron, NIP, CDC has also evaluated and compared measles antibody persistence 5 years after a second dose of measles vaccine given at 4-5 or 11-12 years of age. All children were measles antibody positive at follow-up. Measles neutralizing antibody titers were not significantly lower than titers seen at 6 months after the second dose providing evidence that the 2 dose regimen for measles vaccination provides long term protection. Immunocompromised children cannot receive measles vaccine and depend upon passive protection provided by immunoglobulin products. In collaboration with our colleagues in OBRR, we found that measles neutralizing antibody in IG is predominantly isotype IgG1. In collaboration with Dr. Kleper Almeida, NIH Clinical Center, we evaluated peak and trough measles serum neutralizing antibody titers following administration of IGIV to patients following bone marrow transplant. Interestingly, patients born outside of the US and individuals born in the US prior to 1956 had high levels of measles antibody (GMTs 2664 and 2452, respectively) that were not significantly increased with immunoglobulin administration. In contrast, patients born in the US after 1956 had low levels of measles antibody pre-infusion (GMT, 491)but were able to achieve GMTs greater than 900 following IGIV administration.
