A codon-pair deoptimized live-attenuated vaccine against respiratory syncytial virus is immunogenic and efficacious in non-human primates

Mueller, Steffen; Stauft, Charles B.; Kalkeri, Raj; Koidei, Fusataka; Kushnir, Anna; Tasker, Sybil A.; Coleman, J. Robert

doi:10.1016/j.vaccine.2020.02.056

Cited by 46 publications

(32 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another approach to viral attenuation is known as codon deoptimization, whereby the nucleic acid sequence is modified to use suboptimal codons to encode the wild-type amino acid sequence, which considerably slows the translation of the viral protein during infection. This approach can yield a virus that is highly attenuated in vivo but still able to replicate in vitro if the correct viral protein is selected for deoptimization 92,93 . However, the generation of an attenuated strain of a pathogen for use as a vaccine requires demonstration of its inability to revert genetically to become pathogenic (TABle 1; Box 2).…”

Section: Nature Reviews | Immunologymentioning

confidence: 99%

Immunological considerations for COVID-19 vaccine strategies

et al. 2020

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) outbreak was first reported in Wuhan, China, in late 2019 and, at the time of writing this article, has since spread to 216 countries and territories 1. It has brought the world to a standstill. The respiratory viral pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 20.1 million individuals and killed more than 737,000 people globally, and counting 1. Although physical-distancing a n d o t h er t r a n s m i ss i o n-m i tigation s t r a t e g ies i m p l e m e nted in most countries during the current pandemic have prevented most citizens from being infected, these strategies will paradoxically leave them without immunity to SARS-CoV-2 and thus susceptible to additional waves of infection. Health-care workers, seniors and those with underlying health conditions are at particularly high risk 2-4. It is widely accepted that the world will not return to its prepandemic normalcy until safe and effective vaccines become available and a global vaccination programme is successfully implemented 5. As COVID-19 is new to humankind and the nature of protective immune responses is poorly understood, it is unclear which vaccine strategies will be most successful. Therefore, it is imperative to develop various vaccine platforms and strategies in parallel. Indeed, since the outbreak began, researchers around the world have been racing to develop COVID-19 vaccines, with at least 166 vaccine candidates currently in preclinical and clinical development 5 (Fig. 1). To meet the urgent need for a vaccine, a new pandemic vaccine development paradigm has been proposed that compresses the development timeline from 10-15 years to 1-2 years 6. However, there remains a lack of clarity as to what may

show abstract

Section: Nature Reviews | Immunologymentioning

confidence: 99%

Immunological considerations for COVID-19 vaccine strategies

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Codagenix (Farmingdale, NY, USA) and the Serum Institute of India (Pune, India) are co-developing a live-attenuated vaccine candidate against SARS-CoV-2 using rational, computer-aided gene design and chemical synthesis through a process referred to as viral gene deoptimization ( 87 ). A vaccine against respiratory syncytial virus designed using this technique has previously been shown to induce protective immunity in NHPs ( 88 ). The German Center for Infection Research (DZIF, Braunschweig, Germany) and Zydus Cadila (Etna Biotech, Ahmedabad, India) are developing a live attenuated recombinant measles virus (rMV) vectored vaccine against COVID-19.…”

Section: Vaccine Platform Technologiesmentioning

confidence: 99%

The Long Road Toward COVID-19 Herd Immunity: Vaccine Platform Technologies and Mass Immunization Strategies

et al. 2020

View full text Add to dashboard Cite

There is an urgent need for effective countermeasures against the current emergence and accelerating expansion of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of herd immunity by mass vaccination has been a very successful strategy for preventing the spread of many infectious diseases, hence protecting the most vulnerable population groups unable to develop immunity, for example individuals with immunodeficiencies or a weakened immune system due to underlying medical or debilitating conditions. Therefore, vaccination represents one of the most promising counter-pandemic measures to COVID-19. However, to date, no licensed vaccine exists, neither for SARS-CoV-2 nor for the closely related SARS-CoV or Middle East respiratory syndrome-CoV. In addition, a few vaccine candidates have only recently entered human clinical trials, which hampers the progress in tackling COVID-19 infection. Here, we discuss potential prophylactic interventions for SARS-CoV-2 with a focus on the challenges existing for vaccine development, and we review pre-clinical progress and ongoing human clinical trials of COVID-19 vaccine candidates. Although COVID-19 vaccine development is currently accelerated via so-called fast-track programs, vaccines may not be timely available to have an impact on the first wave of the ongoing COVID-19 pandemic. Nevertheless, COVID-19 vaccines will be essential in the future for reducing morbidity and mortality and inducing herd immunity, if SARS-CoV-2 becomes established in the population like for example influenza virus.

show abstract

“…The codon de‐optimized virus is chemically synthesized to retain 100% amino acid sequence identical to the parent virus, but to contain an increased number of CpG and UpA RNA dinucleotides to up‐regulate host responses. Codon‐pair de‐optimization has been used for attenuating RSV [156]. Codagenix and the Serum Institute of India are developing a live attenuated SARS‐CoV‐2 vaccine, using codon de‐optimization technology, building on previous experience with RSV and influenza [157].…”

Section: Live Vaccinesmentioning

confidence: 99%

Vaccines for COVID-19

Tregoning

Brown

Cheeseman

et al. 2020

Clinical and Experimental Immunology

211

204

View full text Add to dashboard Cite

The spread of the virus SARS‐CoV‐2, the cause of COVID‐19 has triggered a tidal wave of vaccine development. In the first 9 months since the virus emerged over 200 vaccines have begun pre‐clinical development, 36 of which have entered clinical trials. This review will cover the platforms under assessment, the immune responses underpinning the vaccines, the results so far and the considerations for the next steps.

show abstract

A codon-pair deoptimized live-attenuated vaccine against respiratory syncytial virus is immunogenic and efficacious in non-human primates

Cited by 46 publications

References 25 publications

Immunological considerations for COVID-19 vaccine strategies

Immunological considerations for COVID-19 vaccine strategies

The Long Road Toward COVID-19 Herd Immunity: Vaccine Platform Technologies and Mass Immunization Strategies

Vaccines for COVID-19

Contact Info

Product

Resources

About