Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and May Elicit NS1-Specific Antibody Responses in Vaccinated Individuals

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, namely 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 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 (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.

Dynamics of Whole Virus and Non-Structural Protein 1 (NS1) IgG Response in Mice Immunized with Two Commercial Tick-Borne Encephalitis Vaccines

“…The results show that FSME-Immun is the only vaccine that elicits an NS1-specific antibody response in mice. Why the Encepur vaccine does not elicit an NS1-specific antibody response, despite containing detectable levels of NS1 antigen [8], remains enigmatic. After FSME-Immun vaccination, the NS1-specific response is much weaker compared Our mouse experiments have shown that three doses representing the complete vaccination scheme are insufficient to elicit detectable levels of NS1-specific antibodies, and this could explain why there was no detection of NS1 antibodies in studies involving participants who received only the basic vaccination scheme consisting of three doses of the vaccine [7,[9][10][11][12].…”

Sleep architecture, obstructive sleep apnea and functional outcomes in adults with a history of Tick-borne encephalitis

“…First of all, the presence of IgG antibodies against TBEV may be a result from previous infection and/or vaccination. Recently, it has been suggested that the presence of TBEV non-structural (NS)-1 antibodies may discriminate between TBEV-infected and TBEV-vaccinated individuals [ 39 , 40 ], but this data has been challenged [ 41 ], and presently, there is no standardized way of determining whether detected TBEV-specific IgG antibodies are a consequence of infection or vaccination. Secondly, the interpretation of the serology test is complicated since the result can be influenced by cross-reacting antibodies from other flaviviruses by vaccination or infection.…”

Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination

“…Patients and healthy controls received up to three doses of FSME Immun ® intramuscularly—first at baseline at enrollment, which took place 11–13 months after HSCT, second after four weeks and third after 9–12 months. Each dose of FSME Immun ® contains 2.4 µg of formalin-inactivated TBE antigen (with the major constituent virus envelope protein E [ 15 ]) of the European TBEV subtype strain Neudörfl, human albumin as stabilizer and aluminum hydroxide as an adjuvant. Peripheral blood mononuclear cells (PBMCs) were sampled at baseline before the first vaccination, one week after the second and one week after the third vaccination.…”