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.

Development of replication-competent viral vectors for HIV vaccine delivery

“…The modest serum antibody titers induced by measles vaccination are significantly lower than produced following a natural infection [106, 107] nevertheless they may reduce the potency of a MeV vector. Strategies to minimize potential effects of pre-existing antibodies might include vaccine administration mucosally [102, 108, 109], using higher doses, or introducing vector modifications such as replacing MeV glycoproteins with those from CDV [110] or a more distantly related virus [111] such as HIV [51]. …”

Applications and challenges of multivalent recombinant vaccines

“…Ironically, immune responses to the vector components could limit the effectiveness of subsequent vaccinations using the same vector. 24 …”

“…intramuscular-intranasal. 24 Scientists have, also, begun to shed light on analyzing data from various HIV vaccine trials conducted, where some (Thailand, RV144) have shown modest success in preventing HIV infection. 31 These analyses are providing some hint as to what type of immune responses may be needed and will help inform future clinical trial design.…”

“…16,17 Live attenuated viral vectors induce strong, long-lasting immune responses against the expressed proteins, including antibody and T cell responses in the blood, and many generate immune responses at mucosal surfaces, depending on their cell targets and sites of replication. 24 Importantly, immune responses immunizations. However, DNA vaccines need to be improved significantly (e.g.…”

Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

“…8 During the past decades, measles virus vaccine strains have emerged oncolytic platform that may not be compromised by preexisting MV immunity. 9 Measles virus vaccine Edmonston or Schwarz strains uses mainly CD46 molecules to infect cells, during cancer development, tumor cells are often selected to express high levels of CD46 molecules, which inhibit the complement system. 10 This CD46 overexpression makes the tumor cells less sensitive to lysis by the complement but highly sensitive to measles vaccine virus infection.…”