Design, immunogenicity and efficacy of a Pan-SARS-CoV-2 synthetic DNA vaccine

Cc, Reed; Schultheis, Katherine; Vm, Andrade; Kalia, Richa; Tur, Jared; Schouest, Blake; Elwood, Dustin; Jn, Walters; Maricic, Igor; Doan, Arthur; Vázquez, Mónica; Eblimit, Zeena; Pezzoli, Patrick; Amante, Dinah; Porto, Maciel; Narvaez, Brandon; M, Lok; Spence, Brittany; Bradette, Heath; Horn, Henry; Yang, Maria; J, Fader; Ferrer, R; Weiner, DB; Kar, Swagata; Jj, Kim; Lm, Humeau; Sj, Ramos; Tr, Smith; Ke, Bibo

doi:10.1101/2021.05.11.443592

Cited by 9 publications

(14 citation statements)

References 54 publications

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“…The limited cross-neutralizing activities of monovalent vaccines against diverse variants might be compensated by a multivalent vaccine, as different variants could offer broad coverage on the key mutations in the RBD region. This is supported by published results that broad immunity against wild type (WT) as well as B.1.1.7, P.1, and B.1.351 variants in a murine model was induced by an antigen representing multiple SARS-CoV-2 variants [ 35 ].…”

Section: Resultssupporting

confidence: 58%

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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Section: Resultssupporting

confidence: 58%

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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“…Further improvements may be achieved by the introduction of mutations that affect S protein topology, such as mutation T343A, which changes the NTD glycan shield and contributes to stabilization of the RBD in the UP-position [199] or the incorporation of motifs that support S protein trimerization [79]. In parallel to the development of VOC-matched vaccines based on the approved vaccines, which is the most straight forward approach as they are easy to produce and will only require basic clinical re-evaluation, studies to explore the concept of a pan-Corona vaccine that can provide protection across all variants, as well as intranasally applied vaccines to boost local mucosal immune responses are being investigated [200][201][202][203].…”

Section: Discussionmentioning

confidence: 99%

Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

et al. 2021

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Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID‑19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.

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“…We recently described the design, immunogenicity, and efficacy of INO-4802, a synthetic DNA vaccine expressing a pan-Spike immunogen aimed at inducing broad immunity across SARS-CoV-2 VOCs [17]. In a hamster challenge model, INO-4802 conferred protection following intranasal challenge with either the Wuhan-Hu-1, B.1.1.7, B.1.351, P.1, or B.1.617.2 (Delta) SARS-CoV-2 variants.…”

Section: Discussionmentioning

confidence: 99%

“…The plasmid designs for INO-4800 and INO-4802 have been previous described [10, 17]. For INO-4802, a SynCon® consensus sequence for the SARS-CoV-2 spike harboring focused RBD mutations and 2P mutation was codon-optimized using Inovio’s proprietary optimization algorithm.…”

Section: Methodsmentioning

confidence: 99%

“…In response to the increasing number of SARS-CoV-2 VOCs demonstrating evasion of vaccine- or infection-induced humoral immunity, we have designed INO-4802, a next-generation DNA vaccine expressing a pan-Spike immunogen which has been shown to raise immunity across SARS-CoV-2 VOCs in mice [17] and confers broad protection in hamsters following intranasal challenge with multiple VOCs [17].…”

Section: Introductionmentioning

confidence: 99%

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Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

Walters

Schouest

Patel

et al. 2021

Preprint

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SUMMARYThe enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.

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Design, immunogenicity and efficacy of a Pan-SARS-CoV-2 synthetic DNA vaccine

Cited by 9 publications

References 54 publications

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

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

Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

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