Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice

Lázaro-Frías, Adrián; Pérez, Patricia; Zamora, Carmen; Sánchez-Cordón, P.J.; Guzmán, María G.; Luczkowiak, Joanna; Delgado, Rafaël; Casasnovas, José M.; Esteban, Mariano; García-Arriaza, Juan

doi:10.1038/s41541-022-00440-w

Cited by 23 publications

(70 citation statements)

References 52 publications

(44 reference statements)

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“…In this investigation, we evaluated the safety, immunogenicity, and efficacy in rhesus macaques of a COVID-19 vaccine candidate based on the poxvirus MVA vector expressing a human codon-optimized full-length SARS-CoV-2 S protein (MVA-S), which was previously reported to induce potent B- and T-cell immune responses and full efficacy in mice ( 16 , 17 , 19 ). Due to the close relatedness of NHPs to humans, inoculation of rhesus macaques with SARS-CoV-2 has been used for current vaccines as a preclinical animal model system, as it leads to a respiratory disease, with virus replication in lungs and in the upper and lower respiratory tracts ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we evaluated the safety, immunogenicity, and efficacy in rhesus macaques of a novel MVA-based vaccine candidate expressing a human codon-optimized full-length SARS-CoV-2 S protein (MVA-S), which was previously reported to induce potent B- and T-cell responses and full efficacy in mice ( 16 , 17 , 19 ). The MVA-S vaccine was well tolerated, and strong binding IgG antibody responses, neutralizing antibodies against parental SARS-CoV-2 and VOC and S-specific IFNγ-producing cells, were induced.…”

Section: Introductionmentioning

confidence: 99%

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Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

et al. 2022

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Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

et al. 2022

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“…The titers of binding anti-S IgG, IgG1, IgG2c, and IgG3 antibodies in individual or pooled sera from immunized C57BL/6 or K18-hACE2 mice were measured by ELISA as previously described ( 20 , 22 , 26 ). Moreover, titers of binding anti-S IgA antibodies were also analyzed in pooled BAL samples.…”

Section: Methodsmentioning

confidence: 99%

“…In particular, we generated COVID-19 vaccine candidates based on the MVA vector expressing either a human codon optimized full-length native spike (S) protein (MVA-CoV2-S and MVA-Δ-CoV2-S) or a full-length S protein stabilized in the prefusion conformation [MVA-CoV2-S(3P)]. Intramuscular administration of one or two doses of these vaccine candidates induced potent SARS-CoV-2-specific T-cell and humoral immune responses in mice, hamsters, or rhesus macaques, as well as full protection against SARS-CoV-2 infection in those animal models ( 16 , 19 , 20 , 22 , 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection

et al. 2022

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Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.

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“…The majority of vaccines against SARS-CoV-2, both approved and in development, include the spike (S) glycoprotein [5][6][7][8]. The trimeric S glycoprotein is made up of two subunits, S1 and S2.…”

Section: Introductionmentioning

confidence: 99%

An S1 subunit vaccine and combination adjuvant (COVAC-1) elicits robust protection against SARS-CoV-2 challenge in African green monkeys

Garnett

Tran

Chan

et al. 2022

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent responsible for the ongoing global pandemic. With over 500 million cases and more than 6 million deaths reported globally, the need for access to effective vaccines is clear. An ideal SARS-CoV-2 vaccine will prevent pathology in the lungs and prevent virus replication in the upper respiratory tract, thus reducing transmission. Here, we assessed the efficacy of an adjuvanted SARS-CoV-2 S1 subunit vaccine, called COVAC-1, in an African green monkey (AGM) model. AGMs immunized and boosted with COVAC-1 were protected from SARS-CoV-2 challenge compared to unvaccinated controls based on reduced pathology and reduced viral RNA levels and infectious virus in the respiratory tract. Both neutralizing antibodies and antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) were observed in vaccinated animals prior to the challenge. COVAC-1 shows effective protection, including in the upper respiratory tract, thus supporting further development and utility for determining the mechanism that confers this protection.

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Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice

Cited by 23 publications

References 52 publications

Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection

An S1 subunit vaccine and combination adjuvant (COVAC-1) elicits robust protection against SARS-CoV-2 challenge in African green monkeys

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