The mRNA-1273 vaccine candidate is capable of triggering an adaptive immune response. This mRNA encodes for the viral spike S-2P antigen. This includes:
- SARS-CoV-2 glycoprotein with a transmembrane anchor that is involved in receptor recognition with ACE2 receptors in host cells.
- an intact S1–S2 cleavage site

According to the article, "S-2P is stabilized in its prefusion conformation by two consecutive proline substitutions at amino acid positions 986 and 987, at the top of the central helix in the S2 subunit." It uses lipid nanoparticle dispersion that contains mRNA encoding the stabilized prefusion SARS-CoV-2 spike protein. The lipid nanoparticle capsule is composed of four lipids and was formulated in a fixed ratio of mRNA and lipid.

- In pre-clinical trials with Rhesus macaque, 10 or 100μg of mRNA-1273 showed successful induction of type 1 helper T-cells (Th1) and no detectable viral antigens over the next few days  
- These non-human primates also showed regression of upper and lower airway infection over the 2 weeks
- mRNA-1273 nucleoside modifications and purification were optimized to stimulate the innate immune system in order to enhance translation and duration. 
- One remaining concern was half-life of antibodies against spike protein. 
- Recent human data shows reduction of antibodies over time after initial infection.

mRNA-1273 Vaccine Specificities

Link to Study: https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

mRNA-1273 Phase I Trial and Results

Link to Study: https://clinicaltrials.gov/ct2/show/NCT04405076?term=NCT04405076&draw=2&rank=1

mRNA-1273 Phase II Trial and Results

mRNA-1273 is a candidate vaccine proposed by Moderna. The candidate vaccine is a lipid nanoparticle that contains an encapsulated, nucleoside-modified messenger RNA (mRNA). The mRNA codes for the SARS-CoV-2 spike (S) glycoprotein stabilized in its prefusion conformation, or the structure it has before it infects a cell. The S glycoprotein is a primary vaccine target as it controls host cell attachment and is needed for viral entry.

Smith College

1. mRNA-1273 (moderna)
2. BNT162b2 (pfizer and biontech)
3. adenovirus type-5 (Ad5)-vectored COVID-19 vaccine (Cansino)
4. rAd26-S and rAd5-S (gamaleya)
5. Ad26.COV2.S (johnson & johnson) 
6. ChAdOx1 (Astrazeneca and Oxford)
7. NVX-CoV2373 (novavax)
8. Inactivated COVID-19 Vaccine (Wuhan Institute of Biological Products)
9. BBIBP-CorV Vaccine (Sinopharm)
10. Sinovac
11. INO-4800 (NCT04336410) by Inovio Pharmaceuticals
12. Anhui Zhifei Longcom and the Chinese Academy of Medical Sciences Vaccine
13. BBV152 (Covaxin)

Phase 3 Vaccine Candidates

- mRNA-1273 is capable of triggering the adaptive immune response. This mRNA essentially codes for the viral spike (S) glycoprotein that is involved in receptor recognition with ACE2 receptors in host cells.
- Uses lipid nanoparticle dispersion that contains mRNA encoding  the stabilized prefusion SARS-CoV-2 spike protein 
- Pre-clinical trials: Rhesus macaque - administration of either 10 or 100 micrograms of the mRNA-1273 showed successful induction of type 1 helper T-cells (Th1)
- In phase 2 of clinical trials and planning on phase 3 later July.
-Supports a two dose (second administration) method of vaccination.

mRNA-1273 COVID-19 Vaccine by ModernaTX, Inc. 

Jackson, L.A. et al. (2020). An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. N Engl J Med. 10:1056. https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

Aimed to further assess the immunogencity and safety of Ad5-vectored COVID-19 vaccine in a larger population with only the 5 x 10^10 and 1 x 10^11 viral particles doses after the first-in-human phase 1 trial with CanSino Biologics (Tianjin, China) suggested high-dose vaccine was associated with a higher risk of severe adverse effects. 
- methods
- results
- discussions
- limitations and future work

Study on immunogenicity and safety of Ad5-vectored COVID-19 vaccine in larger population

mRNA-1273 Vaccine against SARS-CoV-2 Overview

- Ad26.COV2.S is a vaccine candidate designed by Johnson & Johnson.
- It utilizes a non-replicating adenovirus 26 as a vector expressing the stabilized pre-fusion SARS-CoV-2 spike protein.
- It entered Phase 3 clinical testing in late September, becoming the fourth large-scale vaccine in phase 3 in the United States.

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From our Literary Review:
Johnson & Johnson vaccine candidate is phase 1/2a randomized, double blinded, placebo-controlled clinical study. The purpose of the study was to assess the safety, reactogenicity and immunogenicity of the Ad26.COV2.S. Ad26.COV2.S is a non-replicating adenovirus. The safety and immunogenicity data collected after only a single dose are supportive for further clinical development of Ad26.COV2.S.It is a 26 based vector aiming to express the spike protein of SARS-CoV-2. 


Ad26.COV2.S (Johnson& Johnson) Vaccine Overview

- ChAdOx1  are a desirable platform of vaccine because they are immunogenic in older adults and can be manufactured at large scale
- Vaccines made by combining adenoviral vectors, DNA, and poxviral vectors have been used in an attempt to improve immunogenicity--Emergence of antivector immunity inhibits the potency of a second dose, so homologous adenoviral regimens are typically avoided
- "The ChAdOx1 nCoV-19 vaccine (AZD1222) consists of the replication-deficient simian adenovirus vector ChAdOx1, containing the full-length structural surface glycoprotein (spike protein) of SARS-CoV-2, with a tissue plasminogen activator leader sequence. ChAdOx1 nCoV-19 expresses a codon-optimised coding sequence for the spike  protein (GenBank accession number MN908947)."

ChAdOx1 nCoV-19 vaccine by The University of Oxford

- NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimetric full-length SARS-CoV2 spike glycoproteins and Matrix M1 adjuvant
- Novavax identified this as its candidate with high immunogenicity and high levels of neutralizing antibodies
- September 24, 2020: Phase 3 clinical trials began in the UK and immunize 10,000 people in the next 4-6 weeks
- January 21, 2021: 22,000 volunteers enrolled worldwide

NVX-CoV2373 (Novavax) Vaccine Overview

The study aimed to investigate the safety and immunogenicity of an inactivated whole virus vaccine agains SARS-CoV-2. The results of Phase I and Phase II trials suggest that minimal adverse reactions were observed and that a multiple dose approach is needed. Non-human primate trials have been conducted, but large scale clinical trials in humans are needed to understand the efficacy and the potential for long-term adverse reactions.
- Methods
- Results
- Discussion

Inactivated Whole Virus vaccine by Wuhan Institute of Biological Products

This paper summarized the phase 1 and phase 2 trials of an inactivated vaccine against SAR-CoV-2. The safety and immunogenicity of the vaccine were assessed, including the adverse reactions and long term effects of the vaccine.

- Methods
- Results
- Discussion

BBIBP-CorV Vaccine (Sinopharm)

- Sinovac Vaccine is also known as CoronaVac SARS-CoV-2 Vaccine
- this is an inactivated pathogen it differs from how the other rival vaccine candidates are made using either DNA or RNA
- virus is grown in cultures and then inactivated it
- typically takes longer than other vaccines to develop

- Introduction 
- Methods
- Results
- Conclusion

 Sinovac Vaccine

INO-4800 targets the MERS coronavirus Spike protein. The nucleic acid vaccine by attaching to the receptor-binding site and neutralizing the epitopes. The vaccine has initiated a humoral and T-cell response as well as a spike in antibodies which function via competitive inhibition of the ACE2 receptor which the novel coronavirus also binds to. NCT04336410 is optimized through electroporation.

INO-4800 (NCT04336410) by Inovio Pharmaceuticals

From the Literary Review:

The plant based vaccine, CoVLP, uses trimeric spike glycoproteins from Nicotiana benthamiana to mimic the size and shape of SARS-CoV-2 (Ward et al., 2020). Medicago has had previous success utilizing other plant-based vaccines for the Influenza virus and H1N1, so the company decided to develop a VLP vaccine against SARS-CoV-2 as well (Medicago Begins Phase I Clinical Trials for Its COVID-19 Vaccine Candidate, n.d.). A randomized, partially-blinded, prime-boost, 21 days apart, dose escalation phase 1 study determined that the vaccine was well-tolerated and effective when used with adjuvants. Medicago has been approved by the government of Canada to initiate a phase 2/3 trial, which began on November 12, 2020. At the time of writing, CoVLP  is the only plant-based vaccine in phase 3 trials, offering diversity to the pool of vaccine candidates. This added diversity can allow for alternative prophylactic treatment options for those at risk for adverse reactions to other COVID-19 vaccines (Ward et al., 2020).
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CoVLP (Medicago) 

- Background
- Methods
- Results
- Conclusion

CoVLP Phase 1 Trial

- The Anhui Zhifei Longcom vaccine is a recombinant subunit vaccine
- June 19, 2020: approved for phase one clinical trials
- October 22, 2020: complete phase two clinical trials
- Entered Phase 3 clinical trials on November 20, 2020

Anhui Zhifei Longcom and the Chinese Academy of Medical Sciences Vaccine

- BBV152 is an inactivated SARS-CoV-2 vaccine in rhesus macaques. Both Phase 1 and Phase 2 were launched in India. The sponsor is Bharat Biotech International Limited and collaborator is Indian Council of Medical Research.
- Study Description
- Study Design
- Arms and Interventions
- Outcome Measures

BBV152 (Covaxin)

From our Literary Review:

With the aid of the Ministry of Health of the Russian Federation, russian researchers developed a vaccine composed of two distinct adenovirus vector components: recombinant adenovirus type 26 (rAd26) and recombinant adenovirus type 5 (rAd5), each of which had been previously tested separately in clinical trials at Johnson and Johnson (USA) and at the CanSino Biological/Beijing Institute of Biotechnology (China), respectively.  The rAd26/rAd5 vaccine was developed and tested in healthy participants in phase 2 clinical trials after confirming the safety of the two individual vector components in phase 1. They ultimately found  that this heterologous vaccine is safe and immunogenic in healthy adults, but that further investigation is still needed to understand its effectiveness.

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Study on safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19

Investigates the safety and immunogenicity of a heterologous COVID-19 vaccine with two vector components: recombinant adenovirus type 26 (rAd26) and recombinant adenovirus type 5 (rAd5), both of which carry the gene for the SARS-CoV-2 spike glycoprotein S.  This vaccine was developed in two formulations, frozen and lyophilized, and tested in healthy participants after confirming the safety of the two individual vector components in phase 1.  They ultimately find that this heterologous vaccine is safe and immunogenic in healthy adults, but that further investigation is still needed to understand its effectiveness.

- Methods

- Results

- Discussion
  
       
       

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