Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial

Pollard, Andrew J.; Launay, Odile; Lelièvre, Jean‐Daniel; Lacabaratz, Christine; Grande, Sophie; Goldstein, Neil; Robinson, Cynthia; Gaddah, Auguste; Bockstal, Viki; Leyssen, Maarten; Lühn, Kerstin; Richert, Laura; Bétard, Christine; Gibani, Malick M.; Clutterbuck, Elizabeth A.; Snape, Matthew D; Lévy, Yves; Douoguih, Macaya; Thiébaut, Rodolphe; McShane, Christopher; Callendret, Benoît; Dincq, Stéphanie; Ferrault, Camille; Chai, Siew Pin; Gyselen, Maire Paule; Looveren, M. Van; Ballert, Sylvia van; Cnodder, Tinne De; Roza, Len; Forcheh, Chiara; Stevens, Kate; Mastrandrea, Carmela; Ridder, Sanne de; Gundluru, Rachana; Swales, Nathalie; Errijegers, Vanessa; Willems, Wouter F.; Roorda, Veronika; Orzabal, Nicola; Assenberg, Magdalena; Vialatte, Karine; Remblier, Frédéric; Porcar, Elodie; Ottavi, Anton; Destandau, Eugénie; Schwimmer, Christine; Moinot, Laëtitia; Wallet, Cédrick; Allais, Florence; Savel, Hélène; Nedjaai, Naouel; Maugard, Anaïs; Lenzi, Nehza; Loulergue, Pierre; Bahuaud, Mathilde; Lainé, Fabrice; Laviolle, Bruno; Boissel, Nolwenn; Thébault, Elise; Vallée, David; Nicolas, Jean-François; Gilbert, Sophie; Dahel, Karima; Sagorny, Karen; Lucht, F.; Paul, Stéphane; Chanavat, Alice Haccourt; Charra, Florent; Mutter, Catherine; Lambour, Monique; Müller, Caroline; Hutt-Clauss, Anne; Aranda, Olivia; Bernard, Louis; Gissot, Valérie; Hallouin-Bernard, Marie-Charlotte; Goudeau, Alain; Suzzoni, Steve; Auostin, Eva; Brick, Lysiane; López-Zaragoza, José-Luis; Melic, Giovanna; Carvalho, Murial; Chesnel, C.; Hocini, Hakim; Wiedemann, Aurélie; Hanot, Laurent; Rieux, Véronique; Puri, Adeep; Adeloye, Temitope; Boyce, Malcolm; Dennison, Jeremy; Loewenstein, Inge; Sahgal, Omar; Berg, Frans van den; Calvert, W. J.; Faldon, Mary; McClain, Bruce; Newell, Marie-Lousie; Molenberghs, Geert

doi:10.1016/s1473-3099(20)30476-x

Cited by 123 publications

(100 citation statements)

References 21 publications

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“…We showed that RBD and full-length S protein can boost antibody responses as well as or slightly better than an rMVA boost. There is precedent for other heterologous prime−boost systems in which MVA is teamed up with nucleic acids and other virus vectors ( 60 – 62 ), providing another potential vaccine strategy to combat COVID-19.…”

Section: Discussionmentioning

confidence: 99%

One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection

Liu

Americo

Cotter

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Modified vaccinia virus Ankara (MVA) is a replication-restricted smallpox vaccine, and numerous clinical studies of recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases, including COVID-19, are in progress. Here, we characterize rMVAs expressing the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Modifications of full-length S individually or in combination included two proline substitutions, mutations of the furin recognition site, and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) is flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected cells and was recognized by anti-RBD antibody and soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and, upon passive transfer, protected hACE2 transgenic mice from lethal infection with SARS-CoV-2, as well as S-specific CD3+CD8+IFNγ+ T cells. Antibody boosting occurred following a second rMVA or adjuvanted purified RBD protein. Immunity conferred by a single vaccination of hACE2 mice prevented morbidity and weight loss upon intranasal infection with SARS-CoV-2 3 wk or 7 wk later. One or two rMVA vaccinations also prevented detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and greatly reduced induction of cytokine and chemokine mRNAs. A low amount of virus was found in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of low levels of subgenomic mRNAs in turbinates indicated that replication was aborted in immunized animals.

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Section: Discussionmentioning

confidence: 99%

One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection

Liu

Americo

Cotter

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…In the present study, we evaluated rMVA CoV-2 vaccines administered IM with homologous or protein boost protocols. Previous studies have shown enhanced responses when rMVAs were combined with recombinant DNA or other virus vectors (49–51). For example, a filovirus vaccine consisting of an Ad26 vector followed by a rMVA was safe and immunogenic in a phase 2 trial (51).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown enhanced responses when rMVAs were combined with recombinant DNA or other virus vectors (49–51). For example, a filovirus vaccine consisting of an Ad26 vector followed by a rMVA was safe and immunogenic in a phase 2 trial (51). The stability of both Ad26 and rMVA compared to mRNA vaccines, which must be kept frozen except for short periods, is an advantage for global distribution.…”

Section: Discussionmentioning

confidence: 99%

MVA Vector Vaccines Inhibit SARS CoV-2 Replication in Upper and Lower Respiratory Tracts of Transgenic Mice and Prevent Lethal Disease

Liu

Americo

Cotter

et al. 2021

Preprint

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Replication-restricted modified vaccinia virus Ankara (MVA) is a licensed smallpox vaccine and numerous clinical studies investigating recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases have been completed or are in progress. Two rMVA COVID-19 vaccine trials are at an initial stage, though no animal protection studies have been reported. Here, we characterize rMVAs expressing the S protein of CoV-2. Modifications of full length S individually or in combination included two proline substitutions, mutations of the furin recognition site and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected human cells and was recognized by anti-RBD antibody and by soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced S-binding and pseudovirus-neutralizing antibodies. Boosting occurred following a second homologous rMVA but was higher with adjuvanted purified RBD protein. Weight loss and lethality following intranasal infection of transgenic hACE2 mice with CoV-2 was prevented by one or two immunizations with rMVAs or by passive transfer of serum from vaccinated mice. One or two rMVA vaccinations also prevented recovery of infectious CoV-2 from the lungs. A low amount of virus was detected in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of subgenomic mRNA in turbinates on day 2 only indicated that replication was abortive in immunized animals.SignificanceVaccines are required to control COVID-19 during the pandemic and possibly afterwards. Recombinant nucleic acids, proteins and virus vectors that stimulate immune responses to the CoV-2 S protein have provided protection in experimental animal or human clinical trials, though questions remain regarding their ability to prevent spread and the duration of immunity. The present study focuses on replication-restricted modified vaccinia virus Ankara (MVA), which has been shown to be a safe, immunogenic and stable smallpox vaccine and a promising vaccine vector for other infectious diseases and cancer. In a transgenic mouse model, one or two injections of recombinant MVAs that express modified forms of S inhibited CoV-2 replication in the upper and lower respiratory tracts and prevented severe disease.

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“…Zabdeno is the prime vaccination and is an adenovirus type 26 vector expressing the Ebola virus Mayinga variant's glycoprotein. MBA-BN-Filo serves as the boost immunization and is a non-replicating, recombinant, modified vaccinia Ankara (MVA) vector-based vaccine encoding glycoproteins from Zaire Ebola virus, Sudan virus, Marburg virus, and the nucleoprotein from the Tai Forest virus respectively (232).…”

Section: Discussionmentioning

confidence: 99%

Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines

et al. 2021

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The success of inactivated and live-attenuated vaccines has enhanced livestock productivity, promoted food security, and attenuated the morbidity and mortality of several human, animal, and zoonotic diseases. However, these traditional vaccine technologies are not without fault. The efficacy of inactivated vaccines can be suboptimal with particular pathogens and safety concerns arise with live-attenuated vaccines. Additionally, the rate of emerging infectious diseases continues to increase and with that the need to quickly deploy new vaccines. Unfortunately, first generation vaccines are not conducive to such urgencies. Within the last three decades, veterinary medicine has spearheaded the advancement in novel vaccine development to circumvent several of the flaws associated with classical vaccines. These third generation vaccines, including DNA, RNA and recombinant viral-vector vaccines, induce both humoral and cellular immune response, are economically manufactured, safe to use, and can be utilized to differentiate infected from vaccinated animals. The present article offers a review of commercially available novel vaccine technologies currently utilized in companion animal, food animal, and wildlife disease control.

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Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial

Cited by 123 publications

References 21 publications

One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection

One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection

MVA Vector Vaccines Inhibit SARS CoV-2 Replication in Upper and Lower Respiratory Tracts of Transgenic Mice and Prevent Lethal Disease

Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines

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