Broad neutralization against SARS-CoV-2 variants induced by a next-generation protein vaccine V-01

Sun, Shiyu; Chen, Xi; Lin, Jingjing; Ai, Junwen; Yang, Jiaming; Hu, Zhenxiang; Fu, Yang–Xin; Peng, Hua

doi:10.1038/s41421-021-00350-6

Cited by 10 publications

(10 citation statements)

References 10 publications

(3 reference statements)

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“…Interestingly, when we compared the 2-dose immunization regimen with the bivalent vaccine to alternative heterologous immunization regimens, with monovalent D614 followed by monovalent Beta or bivalent vaccines, only the second injection with monovalent Beta induced balanced neutralizing responses, although with a higher variability than 2-doses with the bivalent vaccine. Our data are in line with a previous study in mice showing lower induction of nAbs (parental, Alpha, Beta and Gamma) with heterologous vaccination with S-trimer vaccine (D614 on D0 and Beta on D21), compared to 2-doses with a bivalent vaccine 40 . The limited breadth of responses observed with the 2-doses heterologous regimen contrasts with the expanded breadth of neutralizing responses observed recently after a late booster vaccine in NHPs and humans 14,15 .…”

Section: Discussionsupporting

confidence: 92%

“…To our knowledge, these are the rst data showing extensive cross-neutralization covering all emerging VOC up to 6 months in NHPs after a 2-dose primary immunization. Prior studies showed that bivalent-based or nanoparticle-based vaccine candidates were able to induce balanced neutralizing Ab responses against VOC, but the data were limited to mice or documented on a more limited panel of variants 40,47,48,49 . Other candidates, based on spike-ferritin nanoparticle or RBD-ferritin nanoparticles, showed similar breadth against SARS-CoV-1…”

Section: Discussionmentioning

confidence: 99%

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A Beta-containing bivalent SARS-CoV-2 spike protein vaccine candidate with AS03 elicits durable and broad neutralization of variants including Omicron in macaques and confers protection in hamsters

Berry

Pavot

Anosova

et al. 2022

Preprint

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Background Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC.Methods We conducted immunogenicity and challenge studies in macaques and hamsters using a bivalent recombinant vaccine formulation containing the SARS-CoV-2 prefusion-stabilized Spike trimers of the parental D614 and the Beta (B.1.351) strains with AS03 adjuvant (CoV2 preS dTM-AS03) in a primary immunization setting. Results We show that a primary immunization with the bivalent CoV2 preS dTM-AS03 elicits broader and durable neutralizing antibody responses against VOC including Omicron BA.1, and SARS-CoV-1 as compared to the parental D614 or Beta variant monovalent vaccines in naïve non-human primates. In addition, the bivalent formulation confers protection against viral challenge with SARS-CoV-2 parental D614G strain as well as Alpha and Beta variant strains in hamsters. Conclusions Our findings demonstrate the potential of a Beta-containing bivalent CoV2 preS dTM-AS03 formulation to provide broad and stable immunogenicity, as well as protection against VOC in naïve populations.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

A Beta-containing bivalent SARS-CoV-2 spike protein vaccine candidate with AS03 elicits durable and broad neutralization of variants including Omicron in macaques and confers protection in hamsters

Berry

Pavot

Anosova

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…At the same time, Danmei Su et al also show animals receiving an adjuvanted (antigen plus CpG 1018/alum) boost induced 2-to 4-fold higher nAb titers compared to animals receiving a nonadjuvanted boost (only antigen), suggesting that adjuvants may be needed for achieving an optimal immune response 32 . In our study, it is further demonstrated that appropriate an adjuvant can induced high levels of functional immune responses.…”

Section: Discussionmentioning

confidence: 96%

A potent, broadly protective vaccine against SARS-CoV-2 variants of concern

Wang

Liu

et al. 2022

npj Vaccines

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Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

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“…These data indicate that vaccines based on a single variant may not be sufficient to induce cross-neutralizing activities. Ancestral strain-based vaccines reported to exhibit relatively broad neutralizing activities against SARS-CoV-2 variants also showed relatively diminished cross-reactivity against variants [ 48 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

A Bivalent COVID-19 Vaccine Based on Alpha and Beta Variants Elicits Potent and Broad Immune Responses in Mice against SARS-CoV-2 Variants

Wang

Sun

et al. 2022

Vaccines

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With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants.

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Broad neutralization against SARS-CoV-2 variants induced by a next-generation protein vaccine V-01

Cited by 10 publications

References 10 publications

A Beta-containing bivalent SARS-CoV-2 spike protein vaccine candidate with AS03 elicits durable and broad neutralization of variants including Omicron in macaques and confers protection in hamsters

A Beta-containing bivalent SARS-CoV-2 spike protein vaccine candidate with AS03 elicits durable and broad neutralization of variants including Omicron in macaques and confers protection in hamsters

A potent, broadly protective vaccine against SARS-CoV-2 variants of concern

A Bivalent COVID-19 Vaccine Based on Alpha and Beta Variants Elicits Potent and Broad Immune Responses in Mice against SARS-CoV-2 Variants

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