Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox

Pittman, Phillip R.; Hahn, Matthew W.; Lee, HeeChoon S.; Koca, Craig; Samy, Nathaly; Schmidt, D; Hornung, Joachim; Weidenthaler, Heinz; Heery, Christopher R.; Meyer, Thomas Ph; Silbernagl, Günter; Maclennan, Jane; Chaplin, Paul

doi:10.1056/nejmoa1817307

Cited by 175 publications

(152 citation statements)

References 32 publications

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“…Finally, immunological correlates of protection against smallpox are not known; but it is likely that multiple immune system components including cellular and humoral elements are involved in the protection against smallpox [22]. MVA recently resulted in similar ELISA and PRNT antibody responses as the established replicating vaccinia vaccine, ACAM2000, and it attenuated ACAM2000 cutaneous lesions after vaccination [6].…”

Section: Discussionmentioning

confidence: 99%

Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine

et al. 2020

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Background: Vaccinia is known to induce antibody and cellular responses. Plasmablast, circulating follicular helper T (cTFH) cells, cytokine-expressing CD4 T cells, and memory B cells were compared between subcutaneous (SC) and needle-free jet injection (JI) recipients of non-replicating modified vaccinia Ankara (MVA) vaccine. Methods: Vaccinia-naïve adults received MVA SC or by JI on Days 1 and 29. Vaccinia-specific antibodies were quantified by plaque reduction neutralization test (PRNT) and enzyme-linked immunosorbent assay. Plasmablast, cTFH, and cytokine-expressing CD4 T cells were assessed on Days 1, 8, 15, 29, 36, 43 (cTFH and CD4+ only) and 57. Memory B cells were measured on Days 1 and 57. Results: Of the 36 enrolled subjects, only 22 received both vaccinations and had evaluable specimens after the second vaccine. Plasmablasts peaked one week after each vaccine. Day 15 plasmablasts correlated with peak PRNT titers. cTFH peaked on Days 8 and 36 and correlated with Day 36 plasmablasts. CD4+ peaked at Day 29 and one-third produced ≥2 cytokines. Day 57 memory B cells ranged from 0.1% to 0.17% of IgG-secreting B cells. Conclusions: This study provides insights into the cellular responses to non-replicating MVA, currently used as a vector for a variety of novel vaccines.

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Section: Discussionmentioning

confidence: 99%

Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine

et al. 2020

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“…MVA is the most widely explored of these vectors. Having been attenuated by more than 570 passages in chick embryo fibroblast cells, MVA has a well established safety record, including in individuals who are immunocompromised, and has recently been approved as a vaccine against smallpox 88,89 . NYVAC was engineered by the purposeful deletion of 18 genes involved in host range and pathogenicity; it causes no disseminated disease in immunodeficient mice, like MVA, and is unable to replicate in humans 90 .…”

Section: Vaccine Platforms and Implementationmentioning

confidence: 99%

Prospects for SARS-CoV-2 diagnostics, therapeutics and vaccines in Africa

et al. 2020

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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic, prompting unprecedented efforts to contain the virus. Many developed countries have implemented widespread testing and have rapidly mobilized research programmes to develop vaccines and therapeutics. However, these approaches may be impractical in Africa, where the infrastructure for testing is poorly developed and owing to the limited manufacturing capacity to produce pharmaceuticals. Furthermore, a large burden of HIV-1 and tuberculosis in Africa could exacerbate the severity of infection and may affect vaccine immunogenicity. This Review discusses global efforts to develop diagnostics, therapeutics and vaccines, with these considerations in mind. We also highlight vaccine and diagnostic production platforms that are being developed in Africa and that could be translated into clinical development through appropriate partnerships for manufacture. ✉ e-mail: Emmanuel.

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“…The approval of MVA was also supported by safety studies in subjects with low CD4 counts. Mild to intermediate atopic dermatitis included a phase 3 study [30]. Based on these investigations, Imvanex ® was licensed in all member states of the European Union and in Iceland, Liechtenstein, Canada, and Norway in 2013.…”

Section: Vaccines Against Smallpoxmentioning

confidence: 99%

Smallpox in the Post-Eradication Era

Meyer

Ehmann

Smith

2020

Viruses

110

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Widespread vaccination programmes led to the global eradication of smallpox, which was certified by the World Health Organisation (WHO), and, since 1978, there has been no case of smallpox anywhere in the world. However, the viable variola virus (VARV), the causative agent of smallpox, is still kept in two maximum security laboratories in Russia and the USA. Despite the eradication of the disease smallpox, clandestine stocks of VARV may exist. In a rapidly changing world, the impact of an intentional VARV release in the human population would nowadays result in a public health emergency of global concern: vaccination programmes were abolished, the percentage of immunosuppressed individuals in the human population is higher, and an increased intercontinental air travel allows for the rapid viral spread of diseases around the world. The WHO has authorised the temporary retention of VARV to enable essential research for public health benefit to take place. This work aims to develop diagnostic tests, antiviral drugs, and safer vaccines. Advances in synthetic biology have made it possible to produce infectious poxvirus particles from chemicals in vitro so that it is now possible to reconstruct VARV. The status of smallpox in the post-eradication era is reviewed.

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Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox

Cited by 175 publications

References 32 publications

Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine

Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine

Prospects for SARS-CoV-2 diagnostics, therapeutics and vaccines in Africa

Smallpox in the Post-Eradication Era

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