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SARS-CoV-2 Vaccine Candidates In or Nearing Clinical Trials

Posted on May 6th, 2020 by in COVID-19

The number of vaccines in the pipeline to battle the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reached to >70 candidates [1,2]. Many different vaccination strategies are being tested, even a noncoronavirus-specific candidate (Bacille Calmette-Guerin vaccine) [2,3] is being investigated because of its potential to promote a less inflammatory immune response to respiratory pathogens [2]. However, a SARS-Cov-2–specific vaccine will likely be a better strategy.

Vector Vaccines

The candidate developed by CanSino Biologics Inc and Beijing Institute of Biotechnology (Ad5-nCoV) is the furthest along in the process (approaching phase 2 trials) [4]. These developers are using the same nonreplicating adenovirus (AdV) vector they used to develop their approved Ebola vaccine [5]. The AdV5 vector, often not used because of extensive preexisting immunity in humans [6], showed previous utility in clinical trials when inoculated at high dose (~1010 virions) [7,8]. The immune response to this vaccine was strong but short lived and probably requires a 6-month booster. Although Ad5-EBOV is approved in China for vaccination [5], it might be premature to consider this vector a viable vaccine platform. Because the Ebola outbreak ended before phase 3 trials could begin, this vaccine was not fully vetted.

However, there are 14 more SARS-CoV-2 vaccine candidates that are virus vectors: five are other AdVs (one being a chimp AdV), three are measles viruses, two are influenza viruses, three are poxviruses (one being a horsepox virus), and one is a vesicular stomatitis virus [1]. There is also one bacteria vector (Bifidobacterium longum) called bacTRL-Spike that produces SARS-CoV-2 antigens with its plasmid DNA [9].

Many of these candidates carry the risk of immune destruction before the SARS-CoV-2 immune response adequately develops. The vaccine candidates at less risk are the chimp AdV vector, human AdV26 vector, poxvirus vectors, VSV vector, and bacterial vector (this bacteria is part of our natural flora and gets administered orally). The bacteria vector and the chimp AdV (ChAdOx1) are approaching clinical trials [9,10]. Similar to Ad5-nCov, the ChAdOx1 vaccine (COV001) is also a nonreplicating vector that will be given in a single shot at a similar high dose.

Protein-Based Vaccines

There are also a large number of protein-based vaccine candidates (~29) [1,2]. The candidate furthest along in clinical trials is the one made by Shenzhen Geno-Immune Medical Institute (Covid-19 aAPC) [11]. Its strategy involves using a lentivirus to construct artificial antigen-presenting cells (APCs) to present antigens and then inactivating these cells proliferative capacity. Covid-19 aAPC presents structural and nonstructural SARS-CoV-2 antigens and is administered in three doses.

Another protein-based vaccine candidate is University of Queensland’s spike peptide frozen into prefusion conformation via a molecular clamp. This strategy potentially promotes a strong neutralizing antibody response, but earlier studies showed this technology induced a robust antibody response that was not neutralizing [12].

Another candidate, ImmunoVaccine Technologies DPX-COVID-19, involves a thermostable nanoparticle that presents virus antigens in a fashion that promotes APC activation [13]. This platform was previously used to present B-cell stimulating epitopes (with respiratory syncytial virus) and T-cell stimulating epitopes (for various cancers) [13,14].

Traditional Vaccines

In case these other vaccines don’t work, we have more traditional vaccine candidates in the pipeline (two live attenuated and three killed) [1]. However, these types often take longer to get approved. By the end of the year, we’ll probably be at a better position to determine which vaccines are the better candidates.

Are you involved in COVID-19 vaccine development? To empower your further exploration, Elsevier has launched the Coronavirus Research Hub, aimed to provide you, as an individual researcher, free access to a selection of Elsevier content and services through 28th October 2020. Visit the Research Hub and join your fellow researchers to bring this crisis to an end.

REFERENCES

1. World Health Organization. Draft landscape of COVID-19 candidate vaccines – 11 April 202. Accessed 22 April 202. https://www.who.int/blueprint/priority-diseases/key-action/Novel_Coronavirus_Landscape_nCoV_11April2020.PDF?ua=1

2. Craven J. COVID-19 vaccine tracker. Accessed 22 April 2020. https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker.

3.  ClinicalTrials.gov. Search result for BCG and COVID-19. Accessed 22 April 2020. https://clinicaltrials.gov/ct2/results?cond=BCG%2C+COVID-19&term=&cntry=&state=&city=&dist=&Search=Search

4. ClinicalTrials.gov. A phase II clinical trial to evaluate the recombinant vaccine for COVID-19 (adenovirus vector) (CTII-nCoV). NCT04341389. Accessed 22 April 2020. https://clinicaltrials.gov/ct2/show/NCT04341389?term=vaccine&cond=COVID-19+or+SARS-cov-2&draw=2

5. CanSinoBIO. Pipeline. Accessed 22 April 2020.  http://www.cansinotech.com/homes/article/plist/45.html

6. Rauch S, Jasny E, Schmidt KE, Petsch B.  New vaccine technologies to combat outbreak situations. Front Immunol 2018;9:1963. doi: 10.3389/fimmu.2018.01963.

7. Li JX, Hou LH, Meng FY, et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob Health. 2017;5(3):e324-e334. doi: 10.1016/S2214-109X(16)30367-9.

8. Zhu FC, Wurie AH, Hou LH, et al. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2017;389(10069):621-628. doi: 10.1016/S0140-6736(16)32617-4.

9. ClinicalTrials.gov. Evaluating the safety, tolerability, and immunogenicity of bacTRL-Spike vaccine for prevention of COVID-19. Accessed 22 April 2020. NCT04334980. https://clinicaltrials.gov/ct2/show/NCT04334980?term=vaccine&cond=sars-cov-2&draw=2

10. ClinicalTrials.gov. A study of candidate COVID-19 vaccine (COV001).  Accessed 22 April 2020. NCT04324606. https://clinicaltrials.gov/ct2/show/NCT04324606?term=NCT04324606&draw=2&rank=1

11. ClinicalTrials.gov. Safety and immunity of COVID-19 aAPC vaccine.  Accessed 22 April 2020. NCT04299724. https://clinicaltrials.gov/ct2/show/NCT04299724?cond=NCT04299724&draw=2&rank=1

12. Jaberolansar N, Chappell KJ, Watterson D, et al. Induction of high titred, non-neutralising antibodies by self-adjuvanting peptide epitopes derived from the respiratory syncytial virus fusion protein. Sci Rep. 2017;7(1):11130. doi: 10.1038/s41598-017-10415-w.

13. Karkada M, Berinstein NL, Mansour M. Therapeutic vaccines and cancer: focus on DPX-0907. Biologics. 2014;8:27-38. doi: 10.2147/BTT.S55196.

14. ClinicalTrials.gov. A study to evaluate the safety and reactogenicity of DPX-RSV(A), a respiratory syncytial virus vaccine..  Accessed 22 April 2020. NCT02472548.  https://clinicaltrials.gov/ct2/show/NCT02472548?term=vaccine+dpx&draw=2&rank=5.

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