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Measles Vaccine
1W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
Abstract:
Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9-15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.
Insights
Measles vaccine (MeV) development has focused on attenuation, but the molecular basis for reduced replication and protective immunity remains unclear. Research explores new delivery methods and recombinant MeV vaccines for broader applications.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Measles virus (MeV) remains a significant global child health concern despite existing vaccines.
- Current MeV vaccines are derived from attenuated wild-type strains, with further attenuation achieved through extensive cell culture passages.
- The molecular mechanisms underlying vaccine-induced attenuation and protective immunity are not fully understood.
Purpose of the Study:
- To elucidate the molecular basis of MeV vaccine attenuation and identify immunologic determinants of protective immunity.
- To explore novel vaccine delivery systems, such as inhalation, to overcome challenges in achieving high population immunity.
- To investigate the potential of recombinant MeV vaccines as vectors for other infectious agents and as oncolytic agents.
Main Methods:
- Empirical attenuation of wild-type MeV through in vitro passage in human and chicken cells.
- Analysis of immune responses, including antibody (Ab) and T cell induction, in relation to vaccine efficacy.
- Exploration of reverse genetics for developing recombinant MeV vaccine strains.
Main Results:
- Attenuation correlates with decreased viral replication in lymphoid tissues, though the precise molecular basis is unidentified.
- Immune responses are age-dependent and influenced by maternal antibodies, with protective immunity linked to neutralizing antibody levels.
- Recombinant MeV technology offers potential for novel vaccine vectors and oncolytic therapies.
Conclusions:
- Further research is needed to understand the molecular underpinnings of MeV vaccine attenuation and protective immunity.
- Innovations in vaccine delivery (e.g., inhalation) and recombinant technologies hold promise for enhancing measles control and expanding vaccine applications.
- Despite vaccine availability, sustained high population immunity remains crucial for controlling measles transmission.
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