RELEVANCE OF A PRE-EXISTING MEASLES IMMUNITY PRIOR IMMUNIZATION WITH A RECOMBINANT MEASLES VIRUS VECTOR

Monday, 8th of September 2014

[source]Human Vaccine and Immunotherapeutics[|source]

Novel technologies in vaccinology are necessary to tackle major diseases of today, such as AIDS, malaria and tuberculosis. Reverse genetics permits the designing of viruses, to be used as vectors, in order to deliver foreign antigens to the body. Due to its size, the measles virus (MV) is an excellent vector candidate since its genome allows the incorporation of up to 40% of additional foreign nucleotides.

In this report, authors constructed a MV-based vector containing various HIV-1 and SIV antigens with the ultimate goal of using it as pediatric vaccine against MV and HIV-1 infections. The report documents that MV pre-immunity with neutralization titers up to 500 mIU does not preclude MV replication and can induce significant humoral and cellular immune responses against the vector and the transgene. More details on prime-boost regimen and extrapolation of results are accessible at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891717/

 

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 titres 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.