No abstract

Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection with Borrelia burgdorferi sensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous B. burgdorferi sensu lato infection. The participants received three monthly priming immunizations with either 30 g or 60 g alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected with B. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. NCT01504347.)

Studies evaluating the immunogenicity of two pediatric tick-borne encephalitis virus (TBEV) vaccines have reported contradictory results. These vaccines are based on two different strains of the European TBEV subtype: FSME-Immun Junior is based on the Neudörfl (Nd) strain, whereas Encepur Children is based on the Karlsruhe (K23) strain. The antibody (Ab) response induced by these two vaccines might be influenced by antigenic differences in the envelope (E) protein, which is the major target of neutralizing antibodies. We used an established hybrid virus assay platform to compare the levels of induction of neutralizing antibodies against the two vaccine virus strains in children aged 1 to 11 years who received two immunizations with FSME-Immun Junior or Encepur Children. The influence of amino acid differences between the E proteins of the Nd and K23 vaccine strains was investigated by mutational analyses and three-dimensional computer modeling. FSME-Immun Junior induced 100% seropositivity and similar neutralizing antibody titers against hybrid viruses containing the TBEV E protein of the two vaccine strains. Encepur Children induced 100% seropositivity only against the hybrid virus containing the E protein of the homologous K23 vaccine strain. Antibody responses induced by Encepur Children to the hybrid virus containing the E protein of the heterologous Nd strain were substantially and significantly (P < 0.001) lower than those to the K23 vaccine strain hybrid virus. Structure-based mutational analyses of the TBEV E protein indicated that this is due to a mutation in the DI-DII hinge region of the K23 vaccine strain E protein which may have occurred during production of the vaccine seed virus and which is not present in any wild-type TBE viruses.IMPORTANCE Our data suggest that there are major differences in the abilities of two European subtype pediatric TBEV vaccines to induce antibodies capable of neutralizing heterologous TBEV strains. This is a result of a mutation in the DI-DII hinge region of the E protein of the K23 vaccine virus strain used to manufacture Encepur Children which is not present in the Nd strain used to manufacture FSME-Immun Junior or in any other known naturally occurring TBEVs.

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao. All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

• Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. • The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao • All TBE vaccines except the one from China have similar but not identical immunization sched-ules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir a rapid immunization schedules is also licensed. The Chinese vaccine is giv-en with 2 primary doses 2 weeks apart followed by annual boosters. • All vaccines induce significant immune responses. In the absence of a formal correlate of pro-tection, the presence of neutralizing antibodies is used as a surrogate marker for protection. • Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. • An effectiveness of approximately 99% (years 2000–2006) and 98,7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccina-tion uptake. • Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. • Both - FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.