Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tick-borne Encephalitis Virus Vaccines Contain Non-structural Protein 1 (NS1) Antigen and May Elicit NS1-Specific Antibody Responses in Vaccinated Individuals

Jiri Salat
,
Kamil Mikulasek
,
Osmany Larralde
ORCID logo ,
Petra Pokorna Formanova
,
Ales Chrdle
,
Jan Haviernik
,
Jana Elsterova
,
Dana Teislerova
,
Martin Palus
ORCID logo ,
Ludek Eyer
,
Zbyněk Zdráhal
,
Juraj Petrik
,
Daniel Ruzek
* ORCID logo
Version 1 : Received: 10 February 2020 / Approved: 11 February 2020 / Online: 11 February 2020 (09:10:41 CET)

A peer-reviewed article of this Preprint also exists.

Salat, J.; Mikulasek, K.; Larralde, O.; Pokorna Formanova, P.; Chrdle, A.; Haviernik, J.; Elsterova, J.; Teislerova, D.; Palus, M.; Eyer, L.; Zdrahal, Z.; Petrik, J.; Ruzek, D. Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals. Vaccines 2020, 8, 81. Salat, J.; Mikulasek, K.; Larralde, O.; Pokorna Formanova, P.; Chrdle, A.; Haviernik, J.; Elsterova, J.; Teislerova, D.; Palus, M.; Eyer, L.; Zdrahal, Z.; Petrik, J.; Ruzek, D. Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals. Vaccines 2020, 8, 81.

Abstract

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

Keywords

tick-borne encephalitis; vaccination; NS1; vaccine; flavivirus

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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