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Merge pull request #1182 from rando2/vaccines-novel
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Final changes for resubmission of novel vaccines
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agitter authored Oct 20, 2022
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2 changes: 1 addition & 1 deletion README.md
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| [Diagnostics](https://greenelab.github.io/covid19-review/#diagnostics) | Molecular and Serologic Diagnostic Technologies for SARS-CoV-2| ~#818~ #1094 | Revision in progress | _mSystems_ | [Release](https://github.com/greenelab/covid19-review/releases/tag/diagnostics-v1); [Preprint](https://arxiv.org/abs/2204.12598) |
| [Pharmaceuticals](https://greenelab.github.io/covid19-review/#identification-and-development-of-therapeutics-for-covid-19) | Identification and Development of Therapeutics for COVID-19 | ✔️ | [Published](https://doi.org/10.1128/mSystems.00233-21) 🎉 | _mSystems_ | [Release](https://github.com/greenelab/covid19-review/releases/tag/pharmaceuticals-v3); [Preprint](http://arxiv.org/abs/2103.02723) |
| [Vaccines- Established Platforms](https://greenelab.github.io/covid19-review/#application-of-traditional-vaccine-development-strategies-to-sars-cov-2) | Application of Traditional Vaccine Development Strategies to SARS-CoV-2 | #830 | Submitted | Submitted to _mSystems_ | [Release](https://github.com/greenelab/covid19-review/releases/tag/vaccines-trad-v1); [Preprint](https://arxiv.org/abs/2208.08907) |
| [Vaccines- Novel Platforms](https://greenelab.github.io/covid19-review/#the-coming-of-age-of-nucleic-acid-vaccines-during-covid-19) | The Coming of Age of Nucleic Acid Vaccines during COVID-19 | #830 | Submitted; preprint pending | Submitted to _mSystems_ | [Release](https://github.com/greenelab/covid19-review/releases/tag/vaccines-novel-v1) |
| [Vaccines- Novel Platforms](https://greenelab.github.io/covid19-review/#the-coming-of-age-of-nucleic-acid-vaccines-during-covid-19) | The Coming of Age of Nucleic Acid Vaccines during COVID-19 | #830 | Accepted 🎉 | _mSystems_ | [Release](https://github.com/greenelab/covid19-review/releases/tag/vaccines-novel-v2 |
| [Nutraceuticals](https://greenelab.github.io/covid19-review/#dietary-supplements-and-nutraceuticals-under-investigation-for-covid-19-prevention-and-treatment) | Dietary Supplements and Nutraceuticals Under Investigation for COVID-19 Prevention and Treatment | ✔️ | [Published](https://doi.org/10.1128/mSystems.00122-21) 🎉 | _mSystems_ | [Release](https://github.com/greenelab/covid19-review/releases/tag/nutraceuticals-v2); [Preprint](http://arxiv.org/abs/2102.02250) |
| [Social Determinants of Health](https://greenelab.github.io/covid19-review/#social-factors-influencing-covid-19-exposure-and-outcomes) | TBD | #868 | In prep | In prep for mSystems
| [Methods (Cyberinfrastructure)](https://greenelab.github.io/covid19-review/#an-open-publishing-response-to-the-covid-19-infodemic) | An Open-Publishing Response to the COVID-19 Infodemic | ✔️ | [Published](http://ceur-ws.org/Vol-2976/paper-2.pdf) 🎉 | [DISCO 2021](https://infoqualitylab.org/events/disco2021/) | [Release](https://github.com/greenelab/covid19-review/releases/tag/methods-v4); [Preprint](https://arxiv.org/abs/2109.08633)
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4 changes: 4 additions & 0 deletions build/assets/custom-dictionary.txt
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Expand Up @@ -57,6 +57,7 @@ aldosterone
Alexandropoulos
alfa
Allograft
alphavirus
alphaviruses
altaica
Amazonas
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heparan
hepatoma
hepatotropic
herpesvirus
Herst
heterologous
HGCO
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infectable
infective
infectivity
inflammasome
infodemic
infodemics
injectate
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reticulum
Retinopathy
reuptake
rhabdovirus
rhamnosus
Rhinolophus
rhinorrhea
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2 changes: 1 addition & 1 deletion content/00.front-matter.md
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Expand Up @@ -27,7 +27,7 @@ It is also available as a [PDF]({{manubot.pdf_url_versioned}}).
{% if individual is defined -%}
It represents one section of a larger evolving review on SARS-CoV-2 and COVID-19 available at <https://greenelab.github.io/covid19-review/>
{% else -%}
Snapshots of individual sections have been published [@individual-pathogenesis; @individual-nutraceuticals; @individual-pharmaceuticals; @individual-methods] or posted as preprints [@individual-diagnostics; individual-vaccines-traditional].
Snapshots of individual sections have been published [@individual-pathogenesis; @individual-nutraceuticals; @individual-pharmaceuticals; @individual-methods] or posted as preprints [@individual-diagnostics; @individual-vaccines-traditional; @individual-vaccines-novel].
{% endif -%}
</em></small>

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26 changes: 12 additions & 14 deletions content/24.vaccines-novel.md
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### Abstract

In the 21^st^ century, several emergent viruses have posed a global threat.
Each of these pathogens has emphasized the value of rapid and scalable vaccine development programs.
Each pathogen has emphasized the value of rapid and scalable vaccine development programs.
The ongoing SARS-CoV-2 pandemic has made the importance of such efforts especially clear.

In particular, new biotechnological advances in vaccine design allowed for new advances in vaccines that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns.
New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns.
During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace.
This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics.
For example, the genome of SARS-CoV-2 was available as early as January 2020, allowing for global efforts in the development of DNA and RNA vaccines to begin within two weeks of the international community becoming aware of the new viral threat.
Additionally, these technologies that were previously only theoretical were found to be not only safe but also to have high vaccine efficacy.
This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics; the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within two weeks of the international community becoming aware of the new viral threat.
Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious.

Although historically a slow process, the rapid development of vaccines during the COVID-19 public health crisis reveals a major shift in vaccine technologies.
In this review, we provide historical context for the emergence of these paradigm-shifting vaccines.
Further context is provided in a companion review exploring more established vaccines platforms.
Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies.
Here, we provide historical context for the emergence of these paradigm-shifting vaccines.
We describe several DNA and RNA vaccines and in terms of their efficacy, safety, and approval status.
We also discuss patterns in worldwide distribution.
The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last two decades in particular, and suggest a new era in vaccines against emerging pathogens.
The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last two decades in particular and suggest a new era in vaccines against emerging pathogens.

### Importance

Expand Down Expand Up @@ -159,7 +157,7 @@ Table: DNA vaccines approved in at least one country [@url:https://covid19.track
#### Plasmid-Vectored DNA Vaccines

Many DNA vaccines use a plasmid vector-based approach, where the sequence encoding the antigen(s) against which an immune response is sought are cultivated in a plasmid and delivered directly to an appropriate tissue [@url:https://www.who.int/biologicals/areas/vaccines/dna/en].
Plasmids can also be designed to act as adjuvants by targeting essential regulators of pathways such as the inflammasome or simply just specific cytokines [@doi:10.1358/dot.2018.54.5.2807864; @doi:[10.1371/journal.pone.0231138](https://doi.org/10.1371%2Fjournal.pone.0231138)].
Plasmids can also be designed to act as adjuvants by targeting essential regulators of pathways such as the inflammasome or simply just specific cytokines [@doi:10.1358/dot.2018.54.5.2807864; @doi:10.1371/journal.pone.0231138].
The DNA itself may also stimulate the innate immune response [@doi:10.1046/j.1365-2796.2003.01140.x; @doi:10.3390/vaccines1030225].
Once the plasmid brings the DNA sequence to an antigen-presenting cell (APC), the host machinery can be used to construct antigen(s) from the transported genetic material, and the body can then synthesize antibodies in response [@doi:10.1038/nrg2432].
The vectors are edited to remove extra sequences [@doi:10.3390/vaccines1030225].
Expand Down Expand Up @@ -296,7 +294,7 @@ The JNJ-78436735 candidate was selected for its favorable immunogenicity profile
The one- versus two-dose regimen was then tested in volunteers through a phase I/IIa trial [@doi:10.1056/NEJMoa2034201; @doi:10.1056/NEJMoa2117608].
A major difference between this vaccine and the other two in this category is that the S protein immunogen is stabilized in its prefusion conformation, while in the Sputnik V and AstraZeneca vaccines it is not.

As of {{owid_most_recent_date}}, {{owid_non_replicating_viral_vector_count}} viral-vectored vaccines are being distributed in {{owid_non_replicating_viral_vector_countries}} countries (Figure @fig:nrvv-distrib).
As of {{owid_most_recent_date}}, data describing the distribution of {{owid_non_replicating_viral_vector_count}} viral-vectored vaccines in {{owid_non_replicating_viral_vector_countries}} countries are available (Figure @fig:nrvv-distrib).
ChAdOx1 nCoV-19 was first approved for emergency use on December 30, 2020 in the U.K. [@url:https://www.astrazeneca.com/media-centre/press-releases/2020/astrazenecas-covid-19-vaccine-authorised-in-uk.html].
Sputnik V was available soon after, and early as January 2021, Sputnik V had been administered to 1.5 million Russians [@url:https://www.brusselstimes.com/news-contents/world/149039/1-5-million-people-have-received-sputnik-v-vaccine-russia-says-russian-direct-investment-fund-mikhail-murashko] and began distributing doses to other countries within Europe such as Belarus, Bosnia-Herzegovina, Hungary, San Marino, Serbia, and Slovakia [@url:https://www.euronews.com/2021/02/12/hungary-to-begin-using-russia-s-sputnik-v-vaccine-today; @url:https://www.euronews.com/2021/02/24/san-marino-buys-russia-s-sputnik-v-after-eu-vaccine-delivery-delays; @url:https://www.themoscowtimes.com/2020/12/29/belarus-starts-coronavirus-vaccination-with-sputnik-v-a72512].

Expand Down Expand Up @@ -443,7 +441,7 @@ As the first mRNA vaccines to make it to market, these two highly efficacious va

As vaccines were rolled out, one study sought to monitor their effectiveness in a real-world setting.
Between December 2020 and April 2021, this prospective cohort study obtained weekly nasal swabs from 3,975 individuals at high risk of SARS-CoV-2 exposure (health care workers, frontline workers, etc.) within the United States [@doi:10.1056/NEJMoa2107058].
Among these participants, 3,179 (80%) had received at least one dose of an mRNA vaccine, and of those, 2,686(84%) were fully vaccinated, corresponding to 68% of trial participants overall.
Among these participants, 3,179 (80%) had received at least one dose of an mRNA vaccine, and of those, 2,686 (84%) were fully vaccinated, corresponding to 68% of trial participants overall.
For each vaccinated participant (defined here as having received at least dose 1 more than 7 days ago) whose sample tested positive for SARS-CoV-2, they categorized the viral lineage(s) present in the sample as well as in samples from 3-4 unvaccinated individuals matched by site and testing date.
Overall efficacy of mRNA vaccines was estimated at 91% with full vaccination, similar to the reports from the clinical trials.
The occurrence of fevers was also lower in individuals who were partially or fully vaccinated, and the duration of symptoms was approximately 6 days shorter.
Expand Down Expand Up @@ -499,7 +497,7 @@ However, these findings do suggest that boosters will likely be needed as the vi

Many trials have also investigated heterologous boosting approaches.
In particular, the mRNA vaccines are a popular choice for booster doses regardless of primary series.
In general, such approaches have been found to confer favorable immunogenicity relative to homologous boosters (e.g, [@doi:10.1080/14760584.2021.1971522; @doi:10.1056/NEJMoa2116414; @doi:10/hzck; @doi:10.1093/jtm/taab191; @doi:10.1093/infdis/jiac092; @doi:10.1056/NEJMc2203165; @doi:10/gnpjxm] and many other studies).
In general, such approaches have been found to confer favorable immunogenicity relative to homologous boosters (e.g., [@doi:10.1080/14760584.2021.1971522; @doi:10.1056/NEJMoa2116414; @doi:10/hzck; @doi:10.1093/jtm/taab191; @doi:10.1093/infdis/jiac092; @doi:10.1056/NEJMc2203165; @doi:10/gnpjxm] and many other studies).
Due to remaining concerns about rare thromboembolic events, vaccinees who received AstraZeneca for their primary course are advised in some countries to seek a heterologous booster [@url:https://www.ecdc.europa.eu/en/publications-data/overview-eueea-country-recommendations-covid-19-vaccination-vaxzevria-and-scoping], although such guidances are not supported by the evidence, which indicates that the first dose of AstraZeneca is most likely to be linked to these rare events [@doi:10/hzcc].
In general, heterologous boosting with mRNA vaccines elicits a strong immune response.
For patients who received BNT162b2 as a heterologous booster following a ChAdOx1 primary series, the vaccine effectiveness was estimated to be 62.4% initially, dropping to 39.6% after 10 weeks [@doi:10.1056/NEJMoa2119451].
Expand Down Expand Up @@ -557,7 +555,7 @@ One of the downsides of this leap in vaccine technologies, however, is that they
As a result, they are also largely available to residents of wealthy countries, primarily in Europe and North America.<!--Add scatter plot with GDP and RNA doses/population, same for DNA-->
Although the VE of DNA vaccines tends to be lower than that of mRNA vaccines [@doi:10.15585/mmwr.mm7038e1], they still provide excellent protection against severe illness and are much easier to distribute due to less complex demands for storage.
Efforts such as COVAX that aim to expand access to vaccines developed by wealthy countries have not been as successful as hoped [@url:https://www.nytimes.com/2021/08/02/world/europe/covax-covid-vaccine-problems-africa.html].
Fortunately, vaccine development programs using more established technologies have been undertaken in many middle income countries, and those vaccines have been more accessible globally [@individual-vaccines-traditional].
Fortunately, vaccine development programs using more established technologies have been undertaken in many middle-income countries, and those vaccines have been more accessible globally [@individual-vaccines-traditional].
Additionally, efforts to develop new formulations of DNA vaccines in lower- and middle-income countries are increasingly being undertaken [@doi:10.1038/d41587-021-00001-x].

The modular nature of nucleic acid-based vaccine platforms has opened a new frontier in responding to emerging viral illnesses.
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1 change: 1 addition & 0 deletions content/90.back-matter.md
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[@individual-pharmaceuticals]: https://pubmed.ncbi.nlm.nih.gov/34726496/
[@individual-diagnostics]: arxiv:2204.12598
[@individual-vaccines-traditional]: arxiv:2208.08907
[@individual-vaccines-novel]: arxiv:2210.07247
21 changes: 0 additions & 21 deletions content/manual-references.json
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]
}
},
{
"type": "article-journal",
"id": "individual-vaccines-novel",
"author": [
{
"literal": "COVID-19 Review Consortium"
}
],
"issued": {
"date-parts": [
[
2022,
7,
28
]
]
},
"container-title": "Manubot",
"title": "The Coming of Age of Nucleic Acid Vaccines during COVID-19",
"URL": "https://greenelab.github.io/covid19-review/v/3bf0adea3375b10ef9c22359ed279f41f49c02c2/#the-coming-of-age-of-nucleic-acid-vaccines-during-covid-19"
},
{
"type": "article-journal",
"id": "individual-evolution",
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7 changes: 5 additions & 2 deletions content/metadata.yaml
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- Project Administration
- Writing - Review & Editing
- Writing - Original Draft
- Visualization
diagnostics:
order: 1
contributions:
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order: 9
contributions:
- Writing - Review & Editing
- Project Administration
- Software
pathogenesis:
order: 9
contributions:
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email: [email protected]
orcid: 0000-0001-8422-7656
coi:
string: "TBD"
lastapproved: !!str 2021-04-30
string: "None"
lastapproved: !!str 2022-10-11
manuscripts:
pathogenesis:
order: 6
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