Virus-Vectored Ebola Vaccines

Dolzhikova, Inna V.; Tokarskaya, Elizaveta A.; Dzharullaeva, Alina S.; Tukhvatulin, Amir I.; Shcheblyakov, Dmitry V.; Voronina, Olga; Syromyatnikova, S. I.; Борисевич, С. В.; Pantyukhov, V. B.; Babira, V. F.; Колобухина, Л. В.; Naroditsky, Boris S.; Logunov, Denis Y.; Gintsburg, Alexander L.

doi:10.32607/20758251-2017-9-3-4-11

Cited by 25 publications

(15 citation statements)

References 38 publications

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“…To achieve these goals, one of the most attractive options is for vaccines to be based on recombinant viral vectors, which can induce humoral and cellular immune responses and form protective immunity after one or two doses. 15 , 16 Recombinant adenovirus vectors have been used for a long time, with safety confirmed in many clinical studies of various preventive and therapeutic drugs. 17 , 18 , 19 , 20 , 21 , 22 , 23 Moreover, the long-term effects of vectors based on adenoviruses have been investigated, 23 by contrast with newer methods that remain to be studied long term.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Background We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine. Methods We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18–60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov , NCT04436471 and NCT04437875 . Findings Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4 + and 1·3% CD8 + with the frozen formulation, and a median cell proliferation of 1·3% CD4 + and 1·1% CD8 + with the lyophilised formulation. Interpretation The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong...

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…We chose a platform based on the recombinant viral vectors rAd5 for delivering the S glycoprotein, because such vectors can efficiently deliver the transgene to multiple cell types [27, 28], their genome has been fully characterized, they are able to grow to high titers [29], and they can induce a strong humoral and cellular immune response [30, 31].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein

et al. 2019

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The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.

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“…Therefore, the first-generation Ad vectors with low seroprevalence in humans (rare human Ad and non-human Ad vectors) are highly recommended for developing pre-pandemic and pandemic influenza vaccines. First-generation Ad vector-based vaccines for the Ebola virus and SARS-CoV-2 were successfully developed [ 131 , 132 , 133 , 134 , 135 , 136 ]. Third-generation (gutless) Ad vectors have been developed mainly for gene therapy to reduce the host immune response against the Ad vector-transduced cells.…”

Section: Discussionmentioning

confidence: 99%

Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines

et al. 2020

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Ever since the discovery of vaccines, many deadly diseases have been contained worldwide, ultimately culminating in the eradication of smallpox and polio, which represented significant medical achievements in human health. However, this does not account for the threat influenza poses on public health. The currently licensed seasonal influenza vaccines primarily confer excellent strain-specific protection. In addition to the seasonal influenza viruses, the emergence and spread of avian influenza pandemic viruses such as H5N1, H7N9, H7N7, and H9N2 to humans have highlighted the urgent need to adopt a new global preparedness for an influenza pandemic. It is vital to explore new strategies for the development of effective vaccines for pandemic and seasonal influenza viruses. The new vaccine approaches should provide durable and broad protection with the capability of large-scale vaccine production within a short time. The adenoviral (Ad) vector-based vaccine platform offers a robust egg-independent production system for manufacturing large numbers of influenza vaccines inexpensively in a short timeframe. In this review, we discuss the progress in the development of Ad vector-based influenza vaccines and their potential in designing a universal influenza vaccine.

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Virus-Vectored Ebola Vaccines

Cited by 25 publications

References 38 publications

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

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

Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein

Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines

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