- inactivated vaccine in healthy adults taken between ages 18-59 years
- randomized double-blind and placebo controlled trial 
- purpose was to evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine
- evaluation for optimal dose

Introduction to Phase 2 Clinical Trial of Sinovac

- 600 healthy adults in the age ranges 18-59 were taken into this study
- each adult was assigned at random to receive two injections of different dosages
- dose of 3 μg/0.5 mL or 6 μg /0.5mL
- placebo day 0-14  or 0-28
- data collected after 7 or 28 days
- blood samples were also taken for antibody assay

Methods of Phase 2 Clinical Trial for Sinovac

- vaccine was well-tolerated
- no dosage safety concerns
- adverse reaction were mild in severity
- most reported symptom was pain at the injection site
- overall it showed good immunogencity

Results of the Phase 2 Clinical Trial for Sinovac

- safety and immunogenicity was seen in both schedules and both dosages 
- successful trial and support to conduct phase 3 trial 

Conclusion for Phase 2 Clinical Trial of Sinovac

Safety Profile:
- Two-dose series was well tolerated with no dose-safety concerns
- Adverse reactions were mild, and most commonly reported was pain at injection site

Method:
- Randomized and double-blind, placebo-controlled
- Consisted of 600 participants; all healthy adults with ages ranging from 18-59
- Two-dose series of 0.5 mL, 0.6 mL, or placebo

Performance:
- The smaller dose (0.5 mL), had 92.4% seroconversion after 2 weeks, and 97.4% after 4 weeks
- Antigen binding antibody levels ranged from 23.8 to 65.4 after 28 days depending on dosage and schedule


Sinovac Vaccine Specifics

- 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

San Jose State University

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

Yan-Jun Zhang, Gang Zeng, Hong-Xing Pan, Chang-Gui Li, Biao Kan, Ya-Ling Hu, Hai-Yan Mao, Qian-Qian Xin, Kai Chu, Wei-Xiao Han, Zhen Chen, Rong Tang, Wei-Dong Yin, Xin Chen, Xue-Jie Gong, Chuan Qin, Yuan-Sheng Hu, Xiao-Yong Liu, Guo-Liang Cui, Cong-Bing Jiang, Heng-Ming Zhang, Jing-Xin Li, Min-Nan Yang, Xiao-Juan Lian, Yan Song, Jin-Xing Lu, Xiang-Xi Wang, Miao Xu, Qiang Gao, Feng-Cai Zhu
medRxiv 2020.07.31.20161216; doi: https://doi.org/10.1101/2020.07.31.20161216

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial

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 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.

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

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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