Profiling of measles-specific humoral immunity in individuals following two doses of MMR vaccine using proteome microarrays.

Iana Haralambieva,Richard Kennedy,Diane Grill,Whitney Simon,Nathaniel Warner,Gregory Poland,Inna Ovsyannikova

doi:10.3390/v7031113

Abstract

Introduction: Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy. Methods: We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses. Results: Our findings demonstrate a high seroprevalence of antibodies directed to the measles virus (MV) phosphoprotein (P), nucleoprotein (N), as well as antibodies to the large polymerase (L) protein (fragment 1234 to 1900 AA). Antibodies to these proteins, in addition to anti-F antibodies (and, to a lesser extent, anti-H antibodies), were correlated with neutralizing antibody titer and/or were associated with and predictive of neutralizing antibody response. Conclusion: Our results identify antibodies to specific measles virus proteins and statistical models for monitoring and assessment of measles-specific functional protective immunity in vaccinated individuals.

Highlights

Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy
Many of the measles cases in the recent outbreaks have been due to failure to vaccinate, but primary and secondary vaccine failure play a role in measles susceptibility and outbreaks[12,13,14,15]
For each subcohort, using a procedure approved by the Mayo Clinic Institutional Review Board (IRB) and the local school district, the subjects were recruited using a random selection of individuals eligible by age and documented vaccine status on the school registry rolls, as previously described [47]

Summary

Introduction

Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy. Methods: We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses. Various reports from the literature estimate 2%–10% of vaccinated individuals (with two measles-mumpsrubella/MMR doses) fail to develop a protective measles antibody response, which can result in infection upon exposure [13,16,17,18,19,20,21,22]. Vaccine failure and waning immunity are major concerns, and further studies of the measles vaccine’s immunogenicity and correlates of protection are necessary. An accurate and feasible method for monitoring measles vaccine-induced protective immunity (e.g., functional neutralizing antibodies relevant to protection and/or other correlates of protection) is crucial for achieving measles eradication [23]

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Conclusion