COVID-19-Impfungen: Replizierend oder Nichtreplizierend?

Zusammenfassung

Innovative und wirksame Impfstrategien entwickeln sich zum wichtigsten Hebel zur Bekämpfung der durch SARS-COV-2 ausgelösten globalen Pandemie. Innerhalb weniger Monate wurden durch Wissenschaftler weltweit vielversprechende neue Vakzine entwickelt; hierbei nutzen mehrere Impfstoffe das Prinzip adenoviraler Vektoren zum Einbringen der eigentlich immunogenen Moleküle des SARS-Coronavirus zum Auslösen einer Immunantwort. Die vom russischen Gamaleya-Institut entwickelte COVID-19-Vakzine Sputnik V (Gam-COVID-Vac) nutzt die adenoviralen Vektoren 26 und 5, um das vollständige SARS-Spike-Protein zur Impfung einzubringen, wobei die unterschiedlichen adenoviralen Vektoren mögliche neutralisierende Effekte gegen Adenoviren umgehen und dadurch eine ausreichende Immunogenität auch bei der Zweitimpfung (booster) gewährleisten. Die bisher veröffentlichten Studien werden teils kontrovers diskutiert, u. a. wegen kleiner Fallzahlen in Phase II und früher klinischer Endpunkte in der Phase III. Auch die bisher fehlende Verfügbarkeit der vollständigen Studienprotokolle und Datensätze wurde in der wissenschaftlichen Gemeinschaft zur Kenntnis genommen. Vulnerable Patientengruppen könnten durch eine wie in Brasilien beschriebene erhaltene Vermehrungsfähigkeit der Ad5-Adenoviren oder wie in der Slowakei beobachtete fehlende Chargenreproduzierbarkeit gefährdet werden, ein Wirksamkeitsverlust der Impfung bei Gesunden ist möglich. Die finale Bewertung in einem geordneten Zulassungsverfahren (z. B. EMA) bleibt daher abzuwarten.

Abstract

Innovative and effective vaccination strategies are the most important lever to address the global SARS-COV2 pandemic. Within months scientists all over the world have developed promising new vaccines, many of which use adenoviral vectors to incorporate immunogenic molecules of SARS-coronavirus in order to elicit effective immune responses. The Gamaleya institute developed the COVID-19 vaccine named Sputnik (Gam-COVID-Vac) using adenoviral vectors ad 26 and ad5 to incorporate a full SARS-Spike Protein for vaccination. Two differing vectors enable so called prime-boost, thus avoiding neutralizing effects against the vector itself, ensuring proper immunogenicity against the vaccine. Current available published evidence has raised controversy among small sample sizes in phase II and early endpoints in phase III studies with Sputnik and scientific community took notice that full study protocols and clinical data haven’t been made available yet. Patient subgroups and vaccination efficacy in healthy vaccinated may be at risk in case of partial viral replication of Ad5 vectors or when batch to batch reproducibility is not warranted, as concerns from authorities in Brazil and Slovakia have recently been raised. Final approval by governing health authorities (e. g. EMA) should therefore be awaited.

Schlüsselwörter

SARS-CoV-2 - Sputnik V - Vektorimpfstoffe - COVID-19

Key words

SARS-CoV2 - Sputnik V - Vector-Vaccines - COVID-19

• Literatur

• 1 Andriollo G, Urbani S, Buonomo A. et al. Rapid protocol for irinotecan desensitization: a case report and literature review. Allergo Journal International 2020; 29: 286-288
• 2 Ankermann T, Spindler T, Gerstlauer M. et al CME. Allergie und Impfen – ein Mythos entmystifiziert. Allergies and vaccination: a myth demystified. Allergo J Int 2018; 27: 234-243 317060 de-38m
• 3 Bangerl T, Zahel B, Lueger A. et al. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs: results of an Austrian cohort study. Allergo Journal International 2020; 29: 227-232
• 4 Bork K, Aygören-Pürsün E, Bas M. et al. Guideline: Hereditary angioedema due to C1 inhibitor deficiency. Allergo Journal International 2019; 28: 16-29
• 5 Bradfisch F, Pietsch M, Forchhammer S. et al Anaphylaktische Reaktionen nach Tollwutimpfungen mit Sensibilisierung gegenüber Gelatine – Fallserie und Literaturübersicht. Allergo J Int 2019; 28: 103-106 Case series of anaphylactic reactions after rabies vaccinations with gelatin sensitization. Allergo-Journal 2019; 28: 18. 317060 de-38m
• 6 Can Bostan Ö, Cakmak M, Kaya S. et al. Anaphylaxis to lidocaine and cross-reactivity to articaine and prilocaine with tolerance to bupivacaine. Allergo Journal International 2020; 29
• 7 Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events. Allergo Journal International 2020; 29: 97-125
• 8 Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part II): classifications and current diagnostic and treatment approaches. Allergo Journal International 2020; 29: 139-154
• 9 Herz A, Kopp MV. Anaphylactic reaction at a pizzeria in a 13-year-old female patient. Allergo Journal International 2020; 29: 165-167
• 10 Honda T, Kuriyama K, Kiso K. et al. Incidence rate of severe adverse drug reactions to nonionic contrast media at the National Hospital Organization Osaka National Hospital. Allergo Journal International 2020; 29: 240-244
• 11 Klimek L, Bergmann KC, Brehler R. et al. Practical handling of allergic reactions to COVID-19 vaccines: A position paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and ÖGAI. Allergo Journal International 2021;
• 12 Klimek L, Chaker AM, Cuevas M. Allergische Reaktionen auf COVID-19-Impfungen – Was HNO-Ärzte wissen sollten – Teil 1: Immunologische Grundlagen von Allergien auf Impfstoffe, Immunmechanismen von allergischen und pseudoallergischen Reaktionen; Teil 2: Charakteristika der mRNA-Impfstoffe BNT162b2- und mRNA-1273 zur Prophylaxe von COVID-19 und assoziierte Immunphänomene; Teil 3: Praktische Aspekte der Prophylaxe, Diagnostik und Therapie von Allergien auf COVID-19-Impfstoffe. Laryngorhinootologie 2021; 100: 344-354
• 13 Klimek L, Novak N, Hamelmann E. et al. Severe allergic reactions after COVID-19 vaccination with the Pfizer/BioNTech vaccine in Great Britain and USA: Position statement of the German Allergy Societies: Medical Association of German Allergologists (AeDA), German Society for Allergology and Clinical Immunology (DGAKI) and Society for Pediatric Allergology and Environmental Medicine (GPA). Allergo Journal International 2021; 30: 51-55
• 14 Klimek L, Worm M, Lange L. et al. Management von Anaphylaxie-gefährdeten Patienten während der Covid-19-Pandemie. Allergo Journal International 2020; 29: 16-26
• 15 Mickler M, Drexler K, Schreml S. Wheat-dependent exercise-induced anaphylaxis with Tri-a-14-sensitization as part of a lipid transfer protein syndrome. Allergo Journal International 2020; 29: 9-11
• 16 Mohamed Khazin S, Abdullah D, Liew AKC. et al. IgE-mediated hypersensitivity to chlorhexidine among first-year dental students. Allergo Journal International 2019; 28: 204-208
• 17 Paulmann M, Mockenhaupt M. Severe skin reactions: clinical picture, epidemiology, etiology, pathogenesis, and treatment. Allergo Journal International 2019; 28: 311-326
• 18 Querbach C, Biedermann T, Busch DH. et al. Suspected penicillin allergy: risk assessment using an algorithm as an antibiotic stewardship project. Allergo Journal International 2020; 29: 174-180
• 19 Ring J, Beyer K, Biedermann T. et al. Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Medical Association of German Allergologists (AeDA), the Society of Pediatric Allergology and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Society for Neonatology and Pediatric Intensive Care (GNPI), the German Society of Dermatology (DDG), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Respiratory Society (DGP), the patient organization German Allergy and Asthma Association (DAAB), the German Working Group of Anaphylaxis Training and Education (AGATE). Allergo Journal International 2021; 30: 1-25
• 20 Wurpts G, Aberer W, Dickel H. et al. Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics. Allergo Journal International 2019; 28: 121-151
• 21 Logunov DY, Dolzhikova IV, Shcheblyakov DV. et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet (London, England) 2021; 397: 671-681
• 22 Barouch DH, Kik SV, Weverling GJ. et al. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine 2011; 29: 5203-5209
• 23 Dolzhikova IV, Zubkova OV, Tukhvatulin AI. et al. Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia. Human vaccines & immunotherapeutics 2017; 13: 613-620
• 24 Lu S. Heterologous prime-boost vaccination. Current opinion in immunology 2009; 21: 346-351
• 25 Voysey M, Clemens SAC, Madhi SA. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet (London, England) 2020; 397: 99-111
• 26 Sadoff J, Le Gars M, Shukarev G. et al. Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate: interim results of a phase 1/2a, double-blind, randomized, placebo-controlled trial. MedRxiv (preprint) 2020;
• 27 Zhu FC, Guan XH, Li YH. et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet 2020; 396: 479-488
• 28 Almuqrin A, Davidson AD, Williamson MK. et al. SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription. Genome Medicine 2021; 13: 43
• 29 Liu J, Ewald BA, Lynch DM. et al. Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys. Journal of virology 2008; 82: 4844-4852
• 30 Logunov DY, Dolzhikova IV, Zubkova OV. et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations two open, non-randomised phase 1/2 studies from Russia. The Lancet 2020; 396: 887-897
• 31 Bucci E. Note of concern. In. Cattivi Scienziati: Cattivi Scienziati-fighting bad and pseudo-science. 2020
• 32 Logunov DY, Dolzhikova IV, Tukhvatullin AI. et al. Safety and efficacy of the Russian COVID-19 vaccine: more information needed – Authors' reply. Lancet (London, England) 2020; 396: e54-e55
• 33 Cohen J. Russia’s claim of a successful COVID-19 vaccine doesn’t pass the ‘smell test,’ critics say. SienceMag.org: SienceMag.org 2020;
• 34 Baraniuk C. Covid-19: What do we know about Sputnik V and other Russian vaccines?. BMJ (Clinical research ed) 2021; 372: n743
• 35 Vilela P. Brazil drug regulator rejects import and use of Sputnik V. In. AgenciaBrasil: Pedro Rafael Vilela. 2021
• 36 EMA. Clarification on Sputnik V vaccine in the EU approval process. In. ema.europa.eu: European Medicines Agency. 2021
• 37 EMA. EMA starts rolling review of the Sputnik V COVID-19 vaccine. In. ema.europa.eu: European Medicines Agency. 2021
• 38 Sheiko I. EU nimmt Sputnik V unter die Lupe. In. dw.com: © 2021 Deutsche Welle. 2021
• 39 OurWorldinData. Coronavirus (COVID-19) Vaccinations. In. Our World in Data: Our World in Data – Statistics and Research. 2021