Quantitative and qualitative features of the antibody response to measles virus

Measles is a leading cause of vaccine-preventable disease worldwide. Most deaths due to measles virus (MV) occur in infants < 12 months. HIV-1 infection is associated with severe measles, higher measles mortality and vaccine failure, and lower levels of transplacental MV-sp antibody.;Neutralizing antibody is the best correlate of protection against measles; however, little is known regarding quality of MV-sp antibody which impacts vaccine efficacy. We determined quantity and quality of antibody responses to measles vaccine in infants < 12 months, to infection and vaccination in HIV-1-infected Zambian children, and to alphavirus-based measles vaccine candidates, formalin-inactivated measles vaccine and live, attenuated measles vaccine, in serum and from B cell clones, in immunized rhesus monkeys.;Infants received measles vaccine at 6 (n=26) or 9 ( n=48) months, followed by a second dose at 12 months, or a single dose at 12 months (n=27) of age. MV-sp IgG levels were lower among infants with maternal antibody. Avidity to measles vaccine was lower at 6 and 9 months versus 12 months, independent of maternal antibody. IgG3 level was highest and H-sp responses were lowest at 6 months; IgG1 was predominant at 12 months. Low avidity at 6 or 9 months did not hinder higher avidity or switching to IgG1 after secondary vaccination at 12 months.;In Zambian children, HIV-1 infection impaired development of MV-sp IgG measured by EIA, but didn't impact neutralization of Chicago-1 MV on Vero or Vero/SLAM cells. Avidity maturation was impaired in HIV-1-infected children at 1- (P=.01) and 3-months (P=.04) following infection, and at 3-months following vaccination (P=.03). Avidity correlated with neutralization of wild-type MV on Vero/SLAM cells (rho=.78, P<.002). IgG1 levels and N-sp responses predominated; IgG3 developed in response to MV infection.;In rhesus monkeys immunized with measles vaccines, we validated methods for analysis of vaccine efficacy at the B cell clonal level. MV-sp IgG purified from successfully generated B cell clones were characterized for levels and avidities, along with serum IgG from immunized monkeys.;These findings show that quality of antibody to measles is impaired by young age and HIV-1 infection, and have been extended to experimental vaccine testing in rhesus monkeys. This work has implications for development of improved measles immunization strategies and vaccine design.