One of the major goals of the USPHS was regional elimination of measles by the year 2000, a goal that was achieved 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 immunocompromised 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 also have lower levels of passively acquired antibody at birth and as a result 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 due to passively acquired antibody. It is not known if immunization of young infants with or without passive antibody would prime for measles specific immune responses, or if immaturity of the infant immune system contributes significantly to vaccine failure. Also, some studies have suggested that intranasal vaccination may improve immunization take rates in this age group because passive antibody is less likely to interfere with vaccine take when given by the mucosal route. Dr. Hayley Gans, along with Drs. Wong-Chew, Maldonado, DeHovitz and Arvin at Stanford University Medical Center, evaluated and compared T cell and B cell responses to immunization with live attenuated measles vaccine at 12 months of age given subcutaneously or via aerosol. Interestingly, vaccine specific T-cell priming occurred in both groups of children irrespective of route of administration and these responses were not inhibited by the presence of maternal antibody. Seroconversion rates and GMTs were higher in the group given vaccine subcutaneously (100%, GMT 539) vs those immunized by the aerosol route (91%, GMT 233). These results indicated that measles immunization of young infants may be of benefit and efficacy of mucosal immunization deserves further study. We have also provided support to Dr. Sonya Hutchins in her evaluation of an early two-dose schedule for measles immunization in Dade County, Florida. This study demonstrated that 94% of children immunized at 6 and 12 months of age had measles antibody titers that were > or = 1:120mIU vs. 98% of those immunized after the first birthday. A case-control study found that vaccine effectiveness was comparably high in both groups with no endemic measles transmission reported after 1993. This study indicates that an early two-dose schedule may be a good strategy to use to protect high-risk, measles susceptible infants. We participated in a collaborative project initiated by Dr. Afzal, NIBSC to test tissue samples by RT-PCR for the presence of measles virus genome to prove or disprove any relationship between measles immunization and subsequent diagnosis of inflammatory bowel disease (IBD). These studies were completed and submitted for publication. Our lab correctly identified all positive and negative measles control samples and, overall, there was no evidence of measles infection in IBD gut tissue samples. Immunoglobulin products are used for measles prophylaxis of immunosuppressed person who cannot receive live attenuated vaccines. In collaboration with our collegues in OBRR we have tested IG and IGIV to look at levels of measles neutralizing antibody titers in lots made over the last three years. This is part of an ongoing study to determine if measles titers decrease as the proportion of US donor with vaccine induced immunity increases over time. In collaboration with Dr. Karol Cortez, we also measured measles serum neutralizing antibody titers before and after IGIV infusions in individuals undergoing bone marrow transplantation. This was the first study to document serum measles neutralizing antibody levels after immunogolublin adminstration. This study demonstrated that following IGIV administration measles antibody levels were greater than 900mIU, a level associated with protection against infection. These results were published in the Journal of Infectious Diseases.
