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. 2018 Aug 2:9:1756.
doi: 10.3389/fimmu.2018.01756. eCollection 2018.

Immunogenicity and Protection After Vaccination With a Modified Vaccinia Virus Ankara-Vectored Yellow Fever Vaccine in the Hamster Model

Justin G Julander  1 , Marco Testori  2 , Cédric Cheminay  2 , Ariane Volkmann  2
Affiliations

Immunogenicity and Protection After Vaccination With a Modified Vaccinia Virus Ankara-Vectored Yellow Fever Vaccine in the Hamster Model

Justin G Julander et al. Front Immunol. .

Abstract

The highly efficacious live-attenuated 17D yellow fever (YF) vaccine is occasionally associated with rare life-threatening adverse events. Modified vaccinia virus Ankara (MVA), a non-replicating poxvirus, has been used as a vaccine platform to safely deliver various antigens. A MVA-based YF vaccine (MVA-BN-YF) was tested with and without a non-mineral oil adjuvant in a hamster model of lethal YF disease and protective efficacy of this vaccine was compared with the 17D vaccine. The vaccine candidate MVA-BN-YF generated a protective response in hamsters infected with YFV that was comparable to protection by the live 17D vaccine. Similar levels of neutralizing antibody were observed in animals vaccinated with either vaccine alone or vaccine with adjuvant. Significant improvement in survival, weight change, and serum alanine aminotransferase levels were observed in vaccinated hamsters when administered 42 and 14 days prior to challenge with Jimenez YF virus (YFV). Neutralizing antibodies induced by MVA-BN-YF were transferred to naïve hamsters prior to virus challenge. Passive administration of neutralizing antibody 24 h prior to virus infection resulted in significantly improved survival and weight change. A trend toward reduced liver enzyme levels was also observed. MVA-BN-YF, therefore, represents a safe alternative to vaccination with live-attenuated YFV.

Keywords: 17D; hamster; modified vaccinia virus Ankara; neutralizing antibodies; passive immunization; yellow fever.

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Figures

Figure 1
Figure 1
(A) Log10 plaque reduction neutralization titers to YF virus (YFV) were significantly elevated in hamsters vaccinated with MVA-BN YF ± adjuvant or with YF-VAX® compared with animals vaccinated with vehicle [Tris-buffered saline (TBS)] ± adjuvant or untreated normal controls (n = 10/group). (B) Vaccination was protective in animals challenged with YFV and (C) serum levels of alanine aminotransferase on day 6 and (D) time-course weight change was improved in hamsters immunized with MVA-BN YF or YFVAX® (***p < 0.001, when compared with vehicle).
Figure 2
Figure 2
(A) Passive administration of serum from hamsters vaccinated with MVA-BN YF or YF-VAX® resulted in low levels of neutralizing Ab in naïve hamsters (n = 10/group) present 24 h after treatment. (B) Survival of hamsters after passive administration of serum from vaccinated hamsters. Passive transfer was only significantly protective in hamsters receiving a 1:10 dilution of serum from hamsters vaccinated with MVA-BN YF. (C) Serum alanine aminotransferase on 6 days post challenge for individual hamsters passively immunized with various dilutions of immune serum generated after immunization with MVA-BN YF or YF-VAX®. (D) Time-course weight change from 0 to 8 dpi.
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