Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.
In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL85-93-specific CD8+T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines.



While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL85-93/leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL85-93-specific CD8+T cells, and in successive immunization protocols the immunization with the GagL85-93/leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL85-93-specific CD8+T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach.



To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.
Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
Meike
M
Kaulfuß
Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
Ina
I
Wensing
Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
Sonja
S
Windmann
Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
Camilla Patrizia
CP
Hrycak
Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany. wibke.bayer@uni-due.de.
Wibke
0000-0002-5885-5592
W
Bayer
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005622:Friend murine leukemia virus / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D012192:Retroviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination / Q000379:methods*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
Adenovirus based immunization; Attenuated retrovirus; Friend retrovirus; Friend virus; Human adenovirus; Retrovirus; Vaccine