This observation could not be explained by characterizing the humoral adaptive immune response against either TBEV or SARS-CoV-2, as there was no cross-neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 or vice versa. IgG (P? ?0.0001), irrespective of SARS-CoV-2 serostatus. Based on these data, we conclude that this observed association of previous TBEV vaccination and reduced risk of SARS-CoV-2 contamination is likely due to residual confounding factors. The increase in TBEV follow-up antibody titers can be explained by natural TBEV exposure or potential non-specific immune activation upon exposure to various pathogens, including SARS-CoV-2. We believe that these findings, although negative, contribute to the current knowledge on potential cross-immunity against SARS-CoV-2 from previous immunizations. adjusted Odds Ratio, Confidence Interval, Reference category for logistic regression, Severe Acute Respiratory Syndrome Coronavirus 2, Standard Deviation, Tick-Borne Encephalitis Computer virus. No cross-neutralization of TBEV antibodies against SARS-CoV-2 We analysed 26 baseline (T1, March/April 2020) and follow-up (T2, August/September 2020) samples divided into three groups defined above. Group characteristics are summarized in Table ?Table22. Table 2 Characteristics of 26 healthcare workers and their TBEV/SARS-CoV-2 serostatus at time points T1 and T2. Severe Acute Respiratory Syndrome Coronavirus-2, Tick-Borne Encephalitis Computer virus. As expected, all four individuals in group 1 had neutralizing antibodies against SARS-CoV-2 in their follow-up (T2), but not in their baseline (T1) sample (Fig.?1a, blue). However, none of the sera from group 2 exhibited any cross-neutralization against SARS-CoV-2 (Fig.?1a, black). Thus, anti-TBEV-antibodies did not have any direct neutralizing effect on SARS-CoV-2 in these samples. Additionally, all four individuals (100%) from group 1 and 16/17 individuals (94%) from group 2 had neutralizing antibodies against TBEV in both baseline and follow-up samples, except for one individual from group 2 who tested unfavorable at T1 but positive at T2. Within the control (group 3), four individuals tested unfavorable for neutralizing antibodies against TBEV as expected, whereas one tested positive at both T1 and T2 (Fig.?1b, red). As individuals were assigned to groups based on their vaccination history, this person is likely to have acquired anti-TBEV antibodies naturally. Overall, neutralizing TBEV antibody titers were significantly higher in the follow-up samples (T2) than in the baseline samples (T1) (P? ?0.0001). However, this pattern was observed in both groups 1 and 2, therefore these results do not allow for any conclusions about a brought on TBEV antibody response due to a recent SARS-CoV-2 contamination. Furthermore, an increase in TBEV neutralizing antibody titer was only observed in 50% of positive samples (11/22). Open in a separate window Physique 1 Serum neutralization test (SNT) revealed MLN 0905 no cross-protection between SARS-CoV-2 and TBEV. (a) Neutralization against SARS-CoV-2 was only observed in convalescent patients (4/4, MLN 0905 blue) and no cross-reactivity was observed in individuals vaccinated against TBEV (black). (b) Neutralization of TBEV was observed in almost all individuals vaccinated against TBEV at T1 (16/17, black) and increased significantly between sampling points (T2, 17/17); ***p?=?0.001. Dashed line: Limit of detection, 1:16 serum dilution. Non-neutralizing samples are assigned the value 10. March/April 2020, August/September 2020, blue: SARS-CoV-2 convalescents, black: TBEV vaccinees, red: unfavorable control group. Significant increase in anti-TBEV IgG titer in follow up samples The qualitative results of anti-TBEV-IgG ELISA are in agreement with the observed serum neutralization test (SNT) results. As observed for neutralizing TBEV antibody titers, anti-TBEV IgG titers determined by ELISA were considerably higher in the follow-up examples (T2, higher titer in 16 of 22 examples) than in Rps6kb1 the baseline examples (T1), (P? ?0.0001), again regardless of SARS-CoV-2 serostatus (Fig.?2a). For IgM, we noticed a tendency towards reducing antibody titers from T1 to T2 for many but two examples. For both of these examples (one each within organizations 1 and 2), IgM seroconversion was noticed, nevertheless at low titers (Fig.?2b). Open up in another window Shape 2 Significant boost was seen in anti-TBEV IgG antibodies in follow-up examples(a) Anti-TBEV IgG antibodies had been significantly improved in follow-up examples in comparison to baseline (T2, 16/22); **** p? ?0.0001. (b) IgM seroconversion was seen in one test with an equivocal upsurge in another. Dashed MLN 0905 lines: Limit of negativity; IgG: 100U/ml, IgM: 10U/ml. March/Apr 2020, August/Sept 2020. Group 1, blue: SARS-CoV-2 convalescents, group 2, dark: TBEV vaccinees, group 3, reddish colored: adverse control group. Dialogue In today’s study, we found out a link between earlier TBEV vaccination and reduced prices of SARS-CoV-2 seroconversion within a prospective cohort of Swiss HCWs. The noticed association cannot be described by any cross-neutralizing aftereffect of anti-TBEV antibodies on SARS-CoV-2. Unexpectedly, anti-TBEV antibody titers improved general between baseline and follow-up examples, regardless of SARS-CoV-2 seroconversion, albeit.
