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

Abstract

Measles virus (MV) vectors are promising candidates for designing new recombinant vaccines since the parental live vaccines have a well-known safety and efficacy record. Like all viral vectors, the MV vector efficacy in inducing a protecting immune answer could be affected by the pre-existing immunity among the human population. In order to determine the optimal immunization route and regimen, we mimicked a MV pre-immunity by passively administrating MV neutralizing antibodies (MV-nAb) prior intramuscular (i.m.) and/or intranasal (i.n.) immunization with recombinant MV expressing the SIV-gag antigen (rMV-SIVgag). Our results revealed that 500 mIU of MV-nAb allowed the induction of a humoral and cellular immune response against the vector and the transgene, while higher titers of the MV-nAb were significantly inhibitory. In a prime-boost regimen, in the presence of MV-nAb, the intranasal-intramuscular (i.n.-i.m.) or intramuscular-intramuscular (i.m.-i.m.) routes induced higher humoral immune responses against the vector and the transgene (SIV-gag). In naive animals, cellular immune response was significantly higher by i.m. immunization; however, MV pre-immunity did not seem to affect the cellular immune response after an i.n. immunization.

In summary, we show that a pre-existing immunity of up to 500 mIU anti-MV neutralizing antibodies had little effect on the replication of rMV and did not inhibit the induction of significant humoral and cellular immune responses in immune-competent mice.

Keywords: :

• vaccine
• pre-existing immunity
• immunization route
• measles
• SIV
• recombinant virus
• reverse genetics
• immune competent mice

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank A. Brogli and Y. Zeller for excellent animal care, and K. Scherler and T. Steiner for skilled technical assistance. This study was performed at Berna Biotech-Crucell with the financial support of NIH grant AI46007 and the NIH contract No. N01-AI-60018 to HYN. We would like to thank Dr Fabian Wild for his generous gift of anti MV antibodies and the NIH AIDS research and reference reagent program for supplying SIV reagents.