Effects of pre-existing orthopoxvirus-specific immunity on the performance of Modified Vaccinia virus Ankara-based influenza vaccines

Arwen F Altenburg,Carolien E Van De Sandt,Dennis De Meulder,Erwin De Bruin,Stella E Van Trierum,Ron A M Fouchier,Marion P G Koopmans,Fiona R M Van Der Klis,Guus F Rimmelzwaan,Rory D De Vries

doi:10.1038/s41598-018-24820-2

Arwen F Altenburg, Carolien E Van De Sandt + Show 8 more

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https://doi.org/10.1038/s41598-018-24820-2

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The replication-deficient orthopoxvirus modified vaccinia virus Ankara (MVA) is a promising vaccine vector against various pathogens and has an excellent safety record. However, pre-existing vector-specific immunity is frequently suggested to be a drawback of MVA-based vaccines. To address this issue, mice were vaccinated with MVA-based influenza vaccines in the presence or absence of orthopoxvirus-specific immunity. Importantly, protective efficacy of an MVA-based influenza vaccine against a homologous challenge was not impaired in the presence of orthopoxvirus-specific pre-existing immunity. Nonetheless, orthopoxvirus-specific pre-existing immunity reduced the induction of antigen-specific antibodies under specific conditions and completely prevented induction of antigen-specific T cell responses by rMVA-based vaccination. Notably, antibodies induced by vaccinia virus vaccination, both in mice and humans, were not capable of neutralizing MVA. Thus, when using rMVA-based vaccines it is important to consider the main correlate of protection induced by the vaccine, the vaccine dose and the orthopoxvirus immune status of vaccine recipients.

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Recombinant viral vectors are under development as novel vaccine candidates that induce immunity to antigens of interest expressed from transgenes
We investigated the performance of rMVA-based influenza vaccines in the presence or absence of pre-existing immunity to orthopoxviruses or influenza virus in mice and evaluated orthopoxvirus-specific immune responses after modified vaccinia virus Ankara (MVA) or vaccinia virus (VACV) vaccination in humans
Induction of orthopoxvirus-specific antibodies upon priming mice with wtMVA or VACV was confirmed by protein array (PA) and ELISA using wtMVA- or VACV-infected cell-lysates as antigens

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Recombinant viral vectors are under development as novel vaccine candidates that induce immunity to antigens of interest expressed from transgenes. Some studies in mice and macaques showed that pre-existing immunity induced by either VACV or MVA had a negative effect on the induction of antigen-specific humoral and/or cellular immune responses by rMVA-based vaccines. Results obtained in humans are contradictory: orthopoxvirus-specific immunity was boosted by multiple rMVA vaccinations and was shown to have a negative effect on the magnitude of the antigen-specific humoral and cellular immune response. In all cases individuals responded to vaccination by either initial induction or boosting of antigen-specific immunity[20,29] This indicates that rMVA-based vaccines remain immunogenic, even in the presence of vector-specific pre-existing immunity. Despite the fact that claims of potential interference by pre-existing vector immunity on immunogenicity of rMVA-based vaccines are made in the literature, the topic has not been addressed sufficiently and studies have led to contradictory results

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