A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Experimental brain infection with cysticercosis in sheep. / Infección experimental cerebral con cisticercosis en ovejas.

OBJECTIVE.: To explore the feasibility of developing a sheep model of neurocysticercosis (NCC) by intracranial infection with T. solium oncospheres. MATERIALS AND METHODS.: We carried out an experimental infection model of NCC in sheep. Approximately 10 T. solium oncospheres previously cultured for 30 days were inoculated intracranially into ten sheep. The oncospheres, in 0.1 mL of physiological saline, were injected into the parietal lobe through an 18-gauge needle. RESULTS.: After three months, granulomas were found in two sheep. In a third sheep we identified a 5 mm diameter cyst in the right lateral ventricle and histological evaluation confirmed that the cyst corresponded to a T. solium larva. Immunohistochemistry with monoclonal antibodies directed against membrane components and excretory/secretory antigens of the T. solium cyst was also used to confirm the etiology of the found granulomas. One of them showed reactivity to the monoclonal antibodies used, thus confirming that it was a cysticercus. CONCLUSION.: This experiment is the proof of concept that it is possible to infect sheep with cysticercosis by intracranial inoculation.

OBJETIVO: . Explorar la viabilidad de desarrollar un modelo de neurocisticercosis (NCC) de oveja mediante infección intracraneal de oncosferas de T. solium. MATERIALES Y MÉTODOS.: Se realizó un modelo de infección experimental de NCC en ovejas. Se inocularon aproximadamente 10 posoncósferas de T. solium cultivadas previamente por 30 días por vía intracraneal en diez ovejas. Las oncósferas, en 0,1 mL de solución salina fisiológica, se inyectaron en el lóbulo parietal a través de una aguja de calibre 18. RESULTADOS.: Después de tres meses, en dos ovejas se encontraron granulomas y en una tercera identificó un quiste de 5 mm de diámetro en el ventrículo lateral derecho y la evaluación histológica confirmó que el quiste corresponde a una larva de T. solium. También se utilizó inmunohistoquímica con anticuerpos monoclonales dirigidos contra componentes de membrana y antígenos excretorios/secretorios del quiste de T. solium para confirmar la etiología de los granulomas encontrados. Uno de ellos mostro reactividad ante los anticuerpos monoclonales utilizados, confirmando así que se trató de un cisticerco. CONCLUSIÓN.: Este experimento es la prueba de concepto de que es posible infectar ovejas con cisticercosis por inoculación intracraneal.

Infección experimental cerebral con cisticercosis en ovejas / Experimental brain infection with cysticercosis in sheep

RESUMEN Objetivo . Explorar la viabilidad de desarrollar un modelo de neurocisticercosis (NCC) de oveja mediante infección intracraneal de oncosferas de T. solium. Materiales y métodos. Se realizó un modelo de infección experimental de NCC en ovejas. Se inocularon aproximadamente 10 posoncósferas de T. solium cultivadas previamente por 30 días por vía intracraneal en diez ovejas. Las oncósferas, en 0,1 mL de solución salina fisiológica, se inyectaron en el lóbulo parietal a través de una aguja de calibre 18. Resultados. Después de tres meses, en dos ovejas se encontraron granulomas y en una tercera identificó un quiste de 5 mm de diámetro en el ventrículo lateral derecho y la evaluación histológica confirmó que el quiste corresponde a una larva de T. solium. También se utilizó inmunohistoquímica con anticuerpos monoclonales dirigidos contra componentes de membrana y antígenos excretorios/secretorios del quiste de T. solium para confirmar la etiología de los granulomas encontrados. Uno de ellos mostro reactividad ante los anticuerpos monoclonales utilizados, confirmando así que se trató de un cisticerco. Conclusión. Este experimento es la prueba de concepto de que es posible infectar ovejas con cisticercosis por inoculación intracraneal.

ABSTRACT Objective. To explore the feasibility of developing a sheep model of neurocysticercosis (NCC) by intracranial infection with T. solium oncospheres. Materials and methods. We carried out an experimental infection model of NCC in sheep. Approximately 10 T. solium oncospheres previously cultured for 30 days were inoculated intracranially into ten sheep. The oncospheres, in 0.1 mL of physiological saline, were injected into the parietal lobe through an 18-gauge needle. Results. After three months, granulomas were found in two sheep. In a third sheep we identified a 5 mm diameter cyst in the right lateral ventricle and histological evaluation confirmed that the cyst corresponded to a T. solium larva. Immunohistochemistry with monoclonal antibodies directed against membrane components and excretory/secretory antigens of the T. solium cyst was also used to confirm the etiology of the found granulomas. One of them showed reactivity to the monoclonal antibodies used, thus confirming that it was a cysticercus. Conclusion. This experiment is the proof of concept that it is possible to infect sheep with cysticercosis by intracranial inoculation.