Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals
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 availab...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/1/81 |
| _version_ | 1798041756613214208 |
|---|---|
| author | Jiri Salat Kamil Mikulasek Osmany Larralde Petra Pokorna Formanova Ales Chrdle Jan Haviernik Jana Elsterova Dana Teislerova Martin Palus Ludek Eyer Zbynek Zdrahal Juraj Petrik Daniel Ruzek |
| author_facet | Jiri Salat Kamil Mikulasek Osmany Larralde Petra Pokorna Formanova Ales Chrdle Jan Haviernik Jana Elsterova Dana Teislerova Martin Palus Ludek Eyer Zbynek Zdrahal Juraj Petrik Daniel Ruzek |
| author_sort | Jiri Salat |
| collection | DOAJ |
| description | 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, namely FSME-IMMUN<sup>®</sup> (Pfizer) and Encepur<sup>®</sup> (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 also detected anti-NS1 antibodies 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 (<i>p </i>< 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. |
| first_indexed | 2024-04-11T22:26:02Z |
| format | Article |
| id | doaj.art-d7efa593a6a34f31bc9b934ddefe33fb |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T22:26:02Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d7efa593a6a34f31bc9b934ddefe33fb2022-12-22T03:59:43ZengMDPI AGVaccines2076-393X2020-02-01818110.3390/vaccines8010081vaccines8010081Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated IndividualsJiri Salat0Kamil Mikulasek1Osmany Larralde2Petra Pokorna Formanova3Ales Chrdle4Jan Haviernik5Jana Elsterova6Dana Teislerova7Martin Palus8Ludek Eyer9Zbynek Zdrahal10Juraj Petrik11Daniel Ruzek12Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicCentral European Institute of Technology, Masaryk University, Kamenice 753/5, CZ-62500 Brno, Czech RepublicThe Jack Copland Centre, Scottish National Blood Transfusion Service, 52 Research Avenue North, Edinburgh EH14 4BE, UKVeterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicHospital Ceske Budejovice, B. Nemcove 585/54, 370 01 Ceske Budejovice, Czech RepublicVeterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicVeterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicHospital Ceske Budejovice, B. Nemcove 585/54, 370 01 Ceske Budejovice, Czech RepublicVeterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicVeterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicCentral European Institute of Technology, Masaryk University, Kamenice 753/5, CZ-62500 Brno, Czech RepublicThe Jack Copland Centre, Scottish National Blood Transfusion Service, 52 Research Avenue North, Edinburgh EH14 4BE, UKVeterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech RepublicVaccination 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, namely FSME-IMMUN<sup>®</sup> (Pfizer) and Encepur<sup>®</sup> (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 also detected anti-NS1 antibodies 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 (<i>p </i>< 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.https://www.mdpi.com/2076-393X/8/1/81tick-borne encephalitisvaccinationns1vaccineflavivirus |
| spellingShingle | Jiri Salat Kamil Mikulasek Osmany Larralde Petra Pokorna Formanova Ales Chrdle Jan Haviernik Jana Elsterova Dana Teislerova Martin Palus Ludek Eyer Zbynek Zdrahal Juraj Petrik Daniel Ruzek Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals Vaccines tick-borne encephalitis vaccination ns1 vaccine flavivirus |
| title | Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals |
| title_full | Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals |
| title_fullStr | Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals |
| title_full_unstemmed | Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals |
| title_short | Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals |
| title_sort | tick borne encephalitis virus vaccines contain non structural protein 1 antigen and may elicit ns1 specific antibody responses in vaccinated individuals |
| topic | tick-borne encephalitis vaccination ns1 vaccine flavivirus |
| url | https://www.mdpi.com/2076-393X/8/1/81 |
| work_keys_str_mv | AT jirisalat tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT kamilmikulasek tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT osmanylarralde tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT petrapokornaformanova tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT aleschrdle tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT janhaviernik tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT janaelsterova tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT danateislerova tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT martinpalus tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT ludekeyer tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT zbynekzdrahal tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT jurajpetrik tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals AT danielruzek tickborneencephalitisvirusvaccinescontainnonstructuralprotein1antigenandmayelicitns1specificantibodyresponsesinvaccinatedindividuals |