Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector

Area of Science:

• * Virology and Immunology
• * Vaccine Development
• * Viral Vector Technology

Background:

• * Measles virus (MV) vectors are promising for recombinant vaccines due to the established safety and efficacy of parental MV vaccines.
• * Pre-existing immunity to viral vectors can potentially hinder vaccine efficacy.
• * Understanding the impact of MV pre-immunity is essential for optimizing immunization strategies.

Purpose of the Study:

• * To determine the optimal immunization route and regimen for recombinant MV vaccines in the presence of pre-existing MV immunity.
• * To investigate the effect of passively administered MV-neutralizing antibodies (MV-nAb) on immune responses to a recombinant MV vector expressing SIV-gag (rMV-SIVgag).

Main Methods:

• * Passive immunization with varying titers of MV-nAb to mimic pre-existing immunity.
• * Intramuscular (i.m.) and/or intranasal (i.n.) immunization with rMV-SIVgag in mice.
• * Evaluation of humoral and cellular immune responses against the vector and SIV-gag transgene.

Main Results:

• * MV-nAb titers up to 500 mIU permitted induction of humoral and cellular immunity against the vector and transgene.
• * Higher MV-nAb titers significantly inhibited immune responses.
• * Prime-boost regimens (i.n.-i.m. or i.m.-i.m.) with MV-nAb enhanced humoral responses; i.m. immunization yielded stronger cellular responses in naive animals.
• * MV pre-immunity did not significantly affect cellular immune responses after i.n. immunization.

Conclusions:

• * A pre-existing immunity level of up to 500 mIU anti-MV neutralizing antibodies minimally affects rMV replication.
• * This level of pre-immunity does not inhibit the induction of significant humoral and cellular immune responses in mice.
• * Findings support the potential of MV vectors for vaccine development, even in populations with prior MV exposure.