TY  - JOUR
AB  - This study aimed to retrospectively assess the cost-effectiveness of various COVID-19 vaccination strategies in Ethiopia. It involved healthcare workers (HCWs) and community participants; and was conducted through interviews and serological tests. Local SARS-CoV-2 variants and seroprevalence rates, as well as national COVID-19 reports and vaccination status were also analyzed. A cost-effectiveness analysis was performed to determine the most economical vaccination strategies in settings with limited vaccine access and high SARS-CoV-2 seroprevalence. Before the arrival of the vaccines, 65% of HCWs had antibodies against SARS-CoV-2, indicating prior exposure to the virus. Individuals with prior infection exhibited a greater antibody response to COVID-19 vaccines and experienced fewer new infections compared to those without prior infection, regardless of vaccination status (5% vs. 24%, p < 0.001 for vaccinated; 3% vs. 48%, p < 0.001 for unvaccinated). The cost-effectiveness analysis indicated that a single-dose vaccination strategy is optimal in settings with high underlying seroprevalence and limited vaccine availability. This study underscores the need for pragmatic vaccination strategies tailored to local contexts, particularly in high-seroprevalence regions, to maximize vaccine impact and minimize the spread of COVID-19. Implementing a targeted approach based on local seroprevalence information could have helped Ethiopia achieve higher vaccination rates and prevent subsequent outbreaks.
AU  - Gudina, E.K.*
AU  - Elsbernd, K.*
AU  - Yilma, D.*
AU  - Kisch, R.*
AU  - Wallrafen-Sam, K.*
AU  - Abebe, G.*
AU  - Mekonnen, Z.*
AU  - Berhane, M.*
AU  - Gerbaba, M.*
AU  - Suleman, S.*
AU  - Mamo, Y.*
AU  - Rubio-Acero, R.*
AU  - Ali, S.*
AU  - Zeynudin, A.*
AU  - Merkt, S.*
AU  - Hasenauer, J.
AU  - Chala, T.K.*
AU  - Wieser, A.*
AU  - Kroidl, A.*
C1  - 71305
C2  - 56039
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Tailoring COVID-19 vaccination strategies in high-seroprevalence settings: Insights from Ethiopia.
JO  - Vaccines
VL  - 12
IS  - 7
PB  - Mdpi
PY  - 2024
ER  - 

TY  - JOUR
AB  - BACKGROUND: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. METHODS: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. RESULTS: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. CONCLUSION: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection.
AU  - Liao, B.H.*
AU  - Platen, L.*
AU  - Grommes, M.*
AU  - Cheng, C.C.*
AU  - Holzmann-Littig, C.*
AU  - Christa, C.*
AU  - Haller, B.*
AU  - Kappler, V.*
AU  - Bester, R.*
AU  - Werz, M.L.*
AU  - Platen, E.*
AU  - Eggerer, P.*
AU  - Tréguer, L.*
AU  - Küchle, C.*
AU  - Schmaderer, C.*
AU  - Heemann, U.*
AU  - Renders, L.*
AU  - Protzer, U.
AU  - Braunisch, M.C.*
C1  - 70376
C2  - 55547
TI  - SARS-CoV-2 neutralization capacity in hemodialysis patients with and without a fifth vaccination with the updated comirnaty original/omicron BA.4-5 vaccine.
JO  - Vaccines
VL  - 12
IS  - 3
PY  - 2024
ER  - 

TY  - JOUR
AB  - ORCHESTRA ("Connecting European Cohorts to Increase Common and Effective Response To SARS-CoV-2 Pandemic") is an EU-funded project which aims to help rapidly advance the knowledge related to the prevention of the SARS-CoV-2 infection and the management of COVID-19 and its long-term sequelae. Here, we describe the early results of this project, focusing on the strengths of multiple, international, historical and prospective cohort studies and highlighting those results which are of potential relevance for vaccination strategies, such as the necessity of a vaccine booster dose after a primary vaccination course in hematologic cancer patients and in solid organ transplant recipients to elicit a higher antibody titer, and the protective effect of vaccination on severe COVID-19 clinical manifestation and on the emergence of post-COVID-19 conditions. Valuable data regarding epidemiological variations, risk factors of SARS-CoV-2 infection and its sequelae, and vaccination efficacy in different subpopulations can support further defining public health vaccination policies.
AU  - Azzini, A.M.*
AU  - Canziani, L.M.*
AU  - Davis, R.J.*
AU  - Mirandola, M.*
AU  - Hoelscher, M.*
AU  - Meyer, L.*
AU  - Laouénan, C.*
AU  - Giannella, M.*
AU  - Rodríguez-Baño, J.*
AU  - Boffetta, P.*
AU  - Mates, D.*
AU  - Malhotra-Kumar, S.*
AU  - Scipione, G.*
AU  - Stellmach, C.*
AU  - Rinaldi, E.*
AU  - Hasenauer, J.
AU  - Tacconelli, E.*
C1  - 67942
C2  - 54420
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - How european research projects can support vaccination strategies: The case of the ORCHESTRA project for SARS-CoV-2.
JO  - Vaccines
VL  - 11
IS  - 8
PB  - Mdpi
PY  - 2023
ER  - 

TY  - JOUR
AB  - Epstein-Barr virus (EBV) is etiologically associated with a number of malignant and non-malignant conditions. Thus, a prophylactic vaccine against this virus could help to reduce the burden of many EBV-associated diseases. Previously, we reported that an EBV virus-like particle (VLP) vaccine was highly immunogenic and produced a strong humoral response in mice. However, since EBV does not infect mice, the efficacy of the VLP in preventing EBV infection could not be addressed. Here we examined, for the first time, the efficacy of the EBV-VLP vaccine using a novel rabbit model of EBV infection. Animals vaccinated with two doses of VLP elicited higher antibody responses to total EBV antigens compared to animals receiving one dose. Vaccinated animals also elicited both IgM and IgG to EBV-specific antigens, VCA and EBNA1. Analysis of peripheral blood and spleen for EBV copy number indicated that the viral load in both of these compartments was lower in animals receiving a 2-dose vaccine. However, the VLP vaccine was ineffective in preventing EBV infection. With several other EBV vaccine candidates currently at various stages of development and testing, we believe that the rabbit model of EBV infection could be a great platform for evaluating potential candidates.
AU  - Reguraman, N.*
AU  - Hassani, A.*
AU  - Philip, P.S.*
AU  - Pich, D.
AU  - Hammerschmidt, W.
AU  - Khan, G.*
C1  - 67646
C2  - 53953
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Assessing the efficacy of VLP-based Vaccine against Epstein-Barr Virus using a rabbit model.
JO  - Vaccines
VL  - 11
IS  - 3
PB  - Mdpi
PY  - 2023
ER  - 

TY  - JOUR
AB  - Here, we investigate the potential of CD70 co-expression during viral vector boost vaccination to improve an antigen-specific T cell response. To determine the chance of activating antigen-specific T cells by CD70, we used the HBV core antigen as a model antigen in a heterologous protein-prime, Modified Vaccinia virus Ankara (MVA) boost vaccination scheme. Both the HBV core and a CD70 expression cassette were co-expressed upon delivery by an MVA vector under the same promoter linked by a P2A site. To compare immunogenicity with and without CD70 co-expression, HBV-naïve, C57BL/6 (wt) mice and HBV-transgenic mice were prime-vaccinated using recombinant HBV core antigen followed by the MVA vector boost. Co-expression of CD70 increased the number of vaccine-induced HBV core-specific CD8 T cells by >2-fold and improved their effector functions in HBV-naïve mice. In vaccinated HBV1.3tg mice, the number and functionality of HBV core-specific CD8 T cells was slightly increased upon CD70 co-expression in low-viremic, but not in high-viremic animals. CD70 co-expression did not impact liver damage as indicated by ALT levels in the serum, but increased the number of vaccine-induced, proliferative T cell clusters in the liver. Overall, this study indicates that orchestrated co-expression of CD70 and a vaccine antigen may be an interesting and safe means of enhancing antigen-specific CD8 T cell responses using vector-based vaccines, although in our study it was not sufficient to break immune tolerance.
AU  - Stephan, A.-S.
AU  - Kosinska, A.
AU  - Mück-Häusl, M.
AU  - Muschaweckh, A.*
AU  - Jager, C.
AU  - Röder, N.
AU  - Heikenwälder, M.
AU  - Dembek, C.J.
AU  - Protzer, U.
C1  - 67514
C2  - 54079
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Evaluation of the effect of CD70 co-expression on CD8 T cell response in protein-prime MVA-boost vaccination in mice.
JO  - Vaccines
VL  - 11
IS  - 2
PB  - Mdpi
PY  - 2023
ER  - 

TY  - JOUR
AB  - Hemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date, it is unclear if hemodialysis patients benefit from four vaccinations. A total of 142 hemodialysis patients received four COVID-19 vaccinations until March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Delta (B.1.617.2), or Omicron (B.1.1.529, sub-lineage BA.1) to determine serum infection neutralization capacity. Four weeks after the fourth vaccination, serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3-1560.8) to 2560.0 (1174.0-2560.0) for the Delta VoC, and from 37.5 (20.0-198.8) to 668.5 (182.2-2560.0) for the Omicron VoC (each p < 0.001) compared to four months after the third vaccination. A significant increase in the neutralization capacity was even observed for patients with high antibody titers after three vaccinations (p < 0.001). Ten patients with SARS-CoV-2 breakthrough infection after the first blood sampling had by trend lower prior neutralization capacity for Omicron (p = 0.051). Our findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron-variants. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients.
AU  - Cheng, C.C.*
AU  - Platen, L.*
AU  - Christa, C.*
AU  - Tellenbach, M.*
AU  - Kappler, V.*
AU  - Bester, R.*
AU  - Liao, B.H.*
AU  - Holzmann-Littig, C.*
AU  - Werz, M.*
AU  - Schönhals, E.*
AU  - Platen, E.*
AU  - Eggerer, P.*
AU  - Tréguer, L.*
AU  - Küchle, C.*
AU  - Schmaderer, C.*
AU  - Heemann, U.*
AU  - Renders, L.*
AU  - Protzer, U.
AU  - Braunisch, M.C.*
C1  - 65977
C2  - 53022
TI  - Improved SARS-CoV-2 neutralization of delta and omicron BA.1 variants of concern after fourth vaccination in hemodialysis patients.
JO  - Vaccines
VL  - 10
IS  - 8
PY  - 2022
ER  - 

TY  - JOUR
AB  - Adoptive cell therapy (ACT) and chimeric antigen receptor (CAR) T cell therapy in particular represents an adaptive, yet versatile strategy for cancer treatment. Convincing results in the treatment of hematological malignancies have led to FDA approval for several CAR T cell therapies in defined refractory diseases. In contrast, the treatment of solid tumors with adoptively transferred T cells has not demonstrated convincing efficacy in clinical trials. One of the main reasons for ACT failure in solid tumors is poor trafficking or access of transferred T cells to the tumor site. Tumors employ a variety of mechanisms shielding themselves from immune cell infiltrates, often translating to only fractions of transferred T cells reaching the tumor site. To overcome this bottleneck, extensive efforts are being undertaken at engineering T cells to improve ACT access to solid tumors. In this review, we provide an overview of the immune cell infiltrate in human tumors and the mechanisms tumors employ toward immune exclusion. We will discuss ways in which T cells can be engineered to circumvent these barriers. We give an outlook on ongoing clinical trials targeting immune cell migration to improve ACT and its perspective in solid tumors.
AU  - Michaelides, S.*
AU  - Obeck, H.*
AU  - Kechur, D.*
AU  - Endres, S.
AU  - Kobold, S.
C1  - 66677
C2  - 53265
TI  - Migratory engineering of T cells for cancer therapy.
JO  - Vaccines
VL  - 10
IS  - 11
PY  - 2022
ER  - 

TY  - JOUR
AB  - During the natural course of chronic hepatitis B virus (HBV) infection, the hepatitis B e antigen (HBeAg) is typically lost, while the direct transmission of HBeAg-negative HBV may result in fulminant hepatitis B. While the induction of HBV-specific immune responses by therapeutic vaccination is a promising, novel treatment option for chronic hepatitis B, it remains unclear whether a loss of HBeAg may influence its efficacy or tolerability. We therefore generated an adeno-associated virus (AAV)-vector that carries a 1.3-fold overlength HBV genome with a typical stop-codon mutation in the pre-core region and initiates the replication of HBeAg(−) HBV in mouse livers. Infection of C57BL/6 mice established persistent HBeAg(−) HBV-replication without any detectable anti-HBV immunity or liver damage. HBV-carrier mice were immunized with TherVacB, a therapeutic hepatitis B vaccine that uses a particulate HBV S and a core protein for prime vaccination, and a modified vaccinia Ankara (MVA) for boost vaccination. The TherVacB immunization of HBeAg(+) and HBeAg(−) HBV carrier mice resulted in the effective induction of HBV-specific antibodies and the loss of HBsAg but only mild liver damage. Intrahepatic, HBV-specific CD8 T cells induced in HBeAg(−) mice expressed more IFNγ but showed similar cytolytic activity. This indicates that the loss of HBeAg improves the performance of therapeutic vaccination by enhancing non-cytolytic effector functions.
AU  - Kosinska, A.
AU  - Festag, J.
AU  - Mück-Häusl, M.
AU  - Festag, M.
AU  - Asen, T.
AU  - Protzer, U.
C1  - 62805
C2  - 51072
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Immunogenicity and antiviral response of therapeutic hepatitis B vaccination in a mouse model of hbeag-negative, persistent hbv infection.
JO  - Vaccines
VL  - 9
IS  - 8
PB  - Mdpi
PY  - 2021
ER  - 

TY  - JOUR
AB  - Viral vectors are promising tools for vaccination strategies and immunotherapies. However, CD8⁺ T cell responses against pathogen-derived epitopes are usually limited to dominant epitopes and antibody responses to recombinant encoded antigens (Ags) are mostly weak. We have previously demonstrated that the timing of viral Ag expression in infected professional Ag-presenting cells strongly shapes the epitope immunodominance hierarchy. T cells recognizing determinants derived from late viral proteins have a clear disadvantage to proliferate during secondary responses. In this work we evaluate the effect of overexpressing the recombinant Ag using the modified vaccinia virus early/late promoter H5 (mPH5). Although the Ag-expression from the natural promoter 7.5 (P7.5) and the mPH5 seemed similar, detailed analysis showed that mPH5 not only induces higher expression levels than P7.5 during early phase of infection, but also Ag turnover is enhanced. The strong overexpression during the early phase leads to broader CD8 T cell responses, while preserving the priming efficiency of stable Ags. Moreover, the increase in Ag-secretion favors the induction of strong antibody responses. Our findings provide the rationale to develop new strategies for fine-tuning the responses elicited by recombinant modified vaccinia virus Ankara by using selected promoters to improve the performance of this viral vector.
AU  - Becker, P.D.*
AU  - Nörder, M.*
AU  - Weissmann, S.*
AU  - Ljapoci, R.*
AU  - Erfle, V.
AU  - Drexler, I.
AU  - Guzman, C.A.*
C1  - 46936
C2  - 39068
SP  - 581-600
TI  - Gene expression driven by a strong viral promoter in MVA increases vaccination efficiency by enhancing antibody responses and unmasking CD8⁺ T cell epitopes.
JO  - Vaccines
VL  - 2
IS  - 3
PY  - 2015
ER  -