Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

Chiuppesi, Flavia; Salazar, Marcela d’Alincourt; Contreras, Heidi; Nguyen, Vu H.; Martinez, Joy; Park, Soo‐Jin; Nguyen, Jenny; Kha, Mindy; Iniguez, Angelina; Zhou, Qiao; Kaltcheva, Teodora; Levytskyy, Roman; Ebelt, Nancy D.; Kang, Tae Hyuk; Wu, Xiwei; Rogers, Thomas F.; Manuel, Edwin R.; Shostak, Yuriy; Diamond, Don J.; Wussow, Felix

doi:10.1101/2020.07.01.183236

Cited by 14 publications

(14 citation statements)

References 55 publications

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“…The animals that receive one or two doses of the MVA-S vaccine were in good health for the whole study(14 days). In addition, the MVA-S vaccine fully protected against SARS-CoV-2 as shown by inhibition of SARS-CoV-2 virus replication in the lungs of vaccinated and infected humanized K18-hACE2 mice, correlating with the morbidity and mortality observed.Others, have recently described the generation of synthetic MVA vectors coexpressing SARS-CoV-2 S and nucleocapsid proteins, showing similar to us the induction of SARS-CoV-2-specific T-cell and humoral responses but not as detail as induced by our MVA-based vaccines candidates; however, they did not define the vaccine efficacy of those synthetic MVA vectors(13).The data presented here demonstrated that MVA-based vaccine candidates expressing the SARS-CoV-2 full-length S protein are highly immunogenic in mice, with a robust activation of both arms of the adaptive immune system, T and B cells. They triggered Th1-skewed immune responses that can facilitate virus clearance without respiratory complications.…”

mentioning

confidence: 59%

“…The envelope S protein mediates virus cell entry through binding to its host receptor, angiotensin-converting enzyme 2 (ACE2) (9), and is the main target for neutralizing antibodies (nAbs) (10)(11)(12). Some vaccine candidates have shown immunogenicity and ability to reduce the severity of disease in preclinical animal models, like mice (13)(14)(15)(16)(17)(18), and non-human primates (NHP) (15,(19)(20)(21)(22). Furthermore, some of the most advanced candidate vaccines, such as those based on adenovirus vectors, mRNA and inactivated SARS-CoV-2 have entered phase I/II clinical trials showing immunogenicity and apparent safety (23,24).…”

Section: Covid-19 Vaccine Development Is Predominantly Based On Sars-mentioning

confidence: 99%

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COVID-19 Vaccine Candidates Based on Modified Vaccinia Virus Ankara Expressing the SARS-CoV-2 Spike Protein Induce Robust T- and B-Cell Immune Responses and Full Efficacy in Mice

García-Arriaza

Garaigorta

Pérez

et al. 2021

J Virol

146

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Vaccines against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are urgently needed. We developed two COVID-19 vaccines based on modified vaccinia virus Ankara (MVA) vectors expressing the entire SARS-CoV-2 spike (S) protein (MVA-CoV2-S); their immunogenicity was evaluated in mice using DNA/MVA or MVA/MVA prime/boost immunizations. Both vaccines induced robust, broad and polyfunctional S-specific CD4+ (mainly Th1) and CD8+ T-cell responses, with a T effector memory phenotype. DNA/MVA immunizations elicited higher T-cell responses. All vaccine regimens triggered high titers of IgG antibodies specific for the S, as well as for the receptor-binding domain; the predominance of the IgG2c isotype was indicative of Th1 immunity. Notably, serum samples from vaccinated mice neutralized SARS-CoV-2 in cell cultures, and those from MVA/MVA immunizations showed a higher neutralizing capacity. Remarkably, one or two doses of MVA-CoV2-S protect humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2. In addition, two doses of MVA-CoV2-S confer full inhibition of virus replication in the lungs. These results demonstrate the robust immunogenicity and full efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic. IMPORTANCE The continuous dissemination of the novel emerging SARS-CoV-2 virus, with more than 78 million infected cases worldwide and higher than 1,700,000 deaths as of December 23, 2020, highlights the urgent need for the development of novel vaccines against COVID-19. With this aim, we have developed novel vaccine candidates based on the poxvirus modified vaccinia virus Ankara (MVA) strain expressing the full-length SARS-CoV-2 spike (S) protein, and we have evaluated their immunogenicity in mice using DNA/MVA or MVA/MVA prime/boost immunization protocols. The results showed the induction of a potent S-specific T-cell response and high titers of neutralizing antibodies. Remarkably, humanized K18-hACE2 mice immunized with one or two doses of the MVA-based vaccine were 100% protected from SARS-CoV-2 lethality. Moreover, two doses of the vaccine prevented virus replication in lungs. Our findings prove the robust immunogenicity and efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.

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mentioning

confidence: 59%

Section: Covid-19 Vaccine Development Is Predominantly Based On Sars-mentioning

confidence: 99%

COVID-19 Vaccine Candidates Based on Modified Vaccinia Virus Ankara Expressing the SARS-CoV-2 Spike Protein Induce Robust T- and B-Cell Immune Responses and Full Efficacy in Mice

García-Arriaza

Garaigorta

Pérez

et al. 2021

J Virol

146

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“…Considering that the lung is a vital organ for SARS-CoV-2 infection, MVA poxviruses have been suggested as potential candidates for COVID-19 vaccine development [ 167 ]. In this context, a novel vaccine platform was developed for MVA, where a unique three-plasmid system can efficiently generate recombinant MVA vectors from chemically synthesized DNA [ 168 ]. Using this technology, mice were immunized with fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 S and nucleocapsid, which elicited robust SARS-CoV-2 antigen-specific humoral and cellular immune responses including potent neutralizing antibodies.…”

Section: Vaccines Against Covid-19mentioning

confidence: 99%

Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19

Lundström¹

2020

Viruses

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Viral vectors can generate high levels of recombinant protein expression providing the basis for modern vaccine development. A large number of different viral vector expression systems have been utilized for targeting viral surface proteins and tumor-associated antigens. Immunization studies in preclinical animal models have evaluated the elicited humoral and cellular responses and the possible protection against challenges with lethal doses of infectious pathogens or tumor cells. Several vaccine candidates for both infectious diseases and various cancers have been subjected to a number of clinical trials. Human immunization trials have confirmed safe application of viral vectors, generation of neutralizing antibodies and protection against challenges with lethal doses. A special emphasis is placed on COVID-19 vaccines based on viral vectors. Likewise, the flexibility and advantages of applying viral particles, RNA replicons and DNA replicon vectors of self-replicating RNA viruses for vaccine development are presented.

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“…One of the best-known poxvirus vectors is the Modified Vaccinia Ankara (MVA), unable to replicate in most mammalian cells, thus becoming a safe vector that expresses antigens which elicit an immune response [ 57 ]. MVA has been recently modified by Chiuppesi et al to co-express SARS-CoV-2 spike (S) and nucleocapsid (N) antigens with the aim of testing its immunogenicity and developing a candidate vaccine against COVID-19.…”

Section: Human Viruses As Preventionmentioning

confidence: 99%

“…For neutralizing experiments, they used SARS-CoV-2 pseudovirus and detected neutralizing antibodies in all vaccine groups receiving the S antigen. The authors claimed that these neutralizing responses increased after the booster immunization [ 57 ].…”

Section: Human Viruses As Preventionmentioning

confidence: 99%

Viral Related Tools against SARS-CoV-2

Fernández-García

Pacios

González-Bardanca

et al. 2020

Viruses

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At the end of 2019, a new disease appeared and spread all over the world, the COVID-19, produced by the coronavirus SARS-CoV-2. As a consequence of this worldwide health crisis, the scientific community began to redirect their knowledge and resources to fight against it. Here we summarize the recent research on viruses employed as therapy and diagnostic of COVID-19: (i) viral-vector vaccines both in clinical trials and pre-clinical phases; (ii) the use of bacteriophages to find antibodies specific to this virus and some studies of how to use the bacteriophages themselves as a treatment against viral diseases; and finally, (iii) the use of CRISPR-Cas technology both to obtain a fast precise diagnose of the patient and also the possible use of this technology as a cure.

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Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

Cited by 14 publications

References 55 publications

COVID-19 Vaccine Candidates Based on Modified Vaccinia Virus Ankara Expressing the SARS-CoV-2 Spike Protein Induce Robust T- and B-Cell Immune Responses and Full Efficacy in Mice

COVID-19 Vaccine Candidates Based on Modified Vaccinia Virus Ankara Expressing the SARS-CoV-2 Spike Protein Induce Robust T- and B-Cell Immune Responses and Full Efficacy in Mice

Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19

Viral Related Tools against SARS-CoV-2

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