138 Understanding protective immunity

Abstract

Measles is the poster child for establishment of life long immunity to re-infection. This is associated with a prolonged persistence of measles virus (MeV) RNA in blood and lymphoid tissue. The live attenuated vaccine is also effective, but the immune responses are less robust and of somewhat shorter duration than after natural infection. Through study of a variety of experimental DNA and virus-vectored vaccines in rhesus macaques followed by wild type MeV challenge, we have identified 4 levels of protective immunity: (1) protection from both rash and viremia; (2) protection from rash, but not viremia; (3) protection from rash and viremia, but not infection; (4) no protection with possibility of enhanced disease. Protection from rash requires high levels of high avidity MeV neutralizing antibody, but this is not sufficient to protect from viremia. MeV-specific T cells alone do not protect from rash or viremia, but lead to more rapid clearance of MeV RNA from blood. Antibody and T cell responses to the hemagglutinin (H) and fusion (F) surface glycoproteins protect from rash and viremia, but not infection leading to late appearance of viral RNA in blood. Parenteral or deep lung respiratory delivery of the live virus vaccine protects against rash, viremia and infection. Further studies are needed to determine if experimental vaccines require additional antigens or induction of a different type of immune response to recapitulate the protection provided by the live attenuated vaccine virus and natural infection.