The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies

Spencer, Alexandra J.; Morris, Susan; Ulaszewska, Marta; Powers, Claire; Kailath, Reshma; Bissett, Cameron; Truby, Adam; Thakur, Nazia; Newman, Joseph; Allen, Elizabeth; Rudiansyah, Indra; Liu, Chang; Dejnirattisai, Wanwisa; Mongkolsapaya, Juthathip; Davies, H. Dele; Donnellan, Francesca R.; Pulido, David; Peacock, Thomas P.; Barclay, William; Bright, Helen; Ren, Kuishu; Screaton, Gavin; McTamney, Patrick M.; Bailey, Dalan; Gilbert, Sarah C.; Lambe, Teresa

doi:10.1016/j.ebiom.2022.103902

Cited by 22 publications

(12 citation statements)

References 46 publications

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“…This was determined based on our previous experience and articles assessing the immunogenicity of adenoviral vectors that had displayed 4 mice per group gives 80% power to detect a two-fold change in T cell or antibody responses. 62 Group sizes were increased to 8 for BALB/c mice to compensate for the potential loss from the development of spontaneous neoplasia which are common in BALB/c mice and unrelated to the experimental procedures. Data were analysed using GraphPad Prism version 9 (GraphPad Software Inc., California, USA).…”

Section: Methodsmentioning

confidence: 99%

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model

Saunders¹,

Gilbride²,

Dowall³

et al. 2023

eBioMedicine

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Section: Methodsmentioning

confidence: 99%

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model

Saunders¹,

Gilbride²,

Dowall³

et al. 2023

eBioMedicine

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“…In the homologous prime/boost of these 2 approved vaccines groups, each was given at four weeks interval. The 4-week gap was used according to the preclinical study protocol of ChAdOX-vectored vaccines 65 , 66 . The goal of experiment 2 was to assess the potential role of ChulaCov19 as a booster in a setting of heterologous primed with other COVID-19 vaccine platforms.…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice

et al. 2023

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Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of “ChulaCov19”, a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP). In female BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 μg elicits robust neutralizing antibody (NAb) and T cell responses in a dose-dependent relationship. The geometric mean titers (GMTs) of NAb against wild-type (WT, Wuhan-Hu1) virus are 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induce better cross-NAb against Delta (B.1.617.2) and Omicron (BA.1 and BA.4/5) variants. This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. In a heterologous prime-boost study, ChulaCov19 booster dose generates a 7-fold increase of NAb against Wuhan-Hu1 WT virus and also significantly increases NAb response against Omicron (BA.1 and BA.4/5) when compared to homologous CoronaVac or AZD1222 vaccination. Challenge studies show that ChulaCov19 protects human-ACE-2-expressing female mice from COVID-19 symptoms, prevents viremia and significantly reduces tissue viral load. Moreover, anamnestic NAb response is undetectable in challenge animals. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or boost vaccination and has entered clinical development.

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“…The primary reason for these small differences appeared to be the level of genetic similarity (homology) between the vaccine antigen and the targeted antibody responses, with the response being more robust when the antigen matches the specific variant. Other studies have also observed strain-specific differential neutralizing responses when comparing the neutralizing capacity induced by Wuhan-Hu-1-specific vaccines with that of variant-adapted vaccine analogs ( 30 , 53 , 56 , 57 ). For example, in Syrian hamsters vaccinated with two IM doses of a multi-antigenic COVID-19 Wuhan-Hu-1-S-specific vaccine candidate based on a synthetic MVA (sMVA) vector or its beta-adapted vaccine analog, it was reported a similar neutralizing activity against the ancestral Wuhan virus in both immunization groups but a higher neutralizing activity against beta and delta variants in hamsters vaccinated with the beta-analog compared with hamsters vaccinated with the COVID-19 Wuhan-Hu-1-specific vaccine candidate ( 30 ).…”

Section: Discussionmentioning

confidence: 93%

“…These results suggest that although approved COVID-19 vaccines can prevent hospitalization and death caused by VoCs, a variant-specific vaccine could ensure better protection against disease and beyond transmission. Therefore, recent research has focused on studying the ability of variant-adapted vaccine analogs to protect against ancestral SARS-CoV-2 and/or SARS-CoV-2 VoCs in different animal models ( 28 , 30 , 31 , 55 – 57 ). We previously reported that immunization with one or two doses of an MVA-based vaccine candidate expressing a human codon-optimized full-length Wuhan-related SARS-CoV-2 S protein, MVA-S, induced robust titers of S- and RBD-binding IgG antibodies and neutralizing antibodies against parental SARS-CoV-2 and VoCs alpha, beta, gamma, delta, and to a lesser extent to omicron, either in mice ( 35 – 37 ), hamsters ( 39 ) or non-human primates ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates

Pérez,

Albericio,

Astorgano

et al. 2023

Front. Immunol.

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The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.1.351) variant, termed MVA-S(3Pbeta). Preclinical evaluation of MVA-S(3Pbeta) in head-to-head comparison to the previously generated MVA-S(3P) vaccine candidate, expressing a full-length prefusion-stabilized Wuhan S protein (with also 3P substitutions), demonstrated that two intramuscular doses of both vaccine candidates fully protected transgenic K18-hACE2 mice from a lethal challenge with SARS-CoV-2 beta variant, reducing mRNA and infectious viral loads in the lungs and in bronchoalveolar lavages, decreasing lung histopathological lesions and levels of proinflammatory cytokines in the lungs. Vaccination also elicited high titers of anti-S Th1-biased IgGs and neutralizing antibodies against ancestral SARS-CoV-2 Wuhan strain and VoCs alpha, beta, gamma, delta, and omicron. In addition, similar systemic and local SARS-CoV-2 S-specific CD4+ and CD8+ T-cell immune responses were elicited by both vaccine candidates after a single intranasal immunization in C57BL/6 mice. These preclinical data support clinical evaluation of MVA-S(3Pbeta) and MVA-S(3P), to explore whether they can diversify and potentially increase recognition and protection of SARS-CoV-2 VoCs.

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The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies

Cited by 22 publications

References 46 publications

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model

Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice

Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates

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