COVID 19 Vaccine Pipeline

In follow up with the earlier posts on the current situation of COVID19 there is an ever increased focussed on the development of a vaccine for the current COVID19 pandemic. As of today, there are 23 candidate vaccines currently in various phase of a clinical trial and another 137 candidates in the preclinical evaluation phase. Vaccine design and development is a long process, though some aspects of it can be fast-tracked in an emergency situation such as the current pandemic. Figure 1 provides with an approximate timeline of events for vaccine development. As you can see depending on the success of each phase a complete market-ready vaccine can still take years of R&D into it.

Figure 1: Vaccine development timeline. Source

There is currently a lack of clarity on various factors of the immune response against SARS CoV2. Though as expected for several viruses, T cell response seems to be important. Studies are currently implying that healthy people have a larger percentage of T cells (Especially helper T cells and Killer T cells) that are reactive to SARS CoV 2 compared to those who are really sick. Interestingly, people who have not been apparently exposed to the virus also have some sort of T cell memory against SARS CoV 2. These are mostly cross-reactive cells, indicating exposure to other coronaviruses. Studies that have looked at the humoral response indicate that though people produce specific antibodies, neutralising antibodies are low in quantity. Several varieties of lymphocytes including CD4+ T cells, CD8+ T cells, B cells, and NK cells have shown a significant association with inflammatory status in COVID-19 CD8+ T cell appears to be the key. Concerns in the rapid deployment of a COVID19 vaccine include the idea that there is a lack of long-term immunity and the possibility of ADE (Antibody-dependent enhancement). The best available picture at present indicates that sterilising immunity and its memory is probably available for about 3-5 months at best, in a natural infection course. In essence, an ideal vaccine has to achieve a longterm neutralising immune response and no ADE.

Here is a summary list of vaccines and some of their features that are currently in one of the clinical testing phases.

Candidate Vaccine	Developer	Design	Evaluation Phase
PiCoVacc	Sinovac	Inactivated SARS CoV 2 CN2 strain with alum	Phase 3
ChAdOx1-S	University of Oxford & AstraZeneca	Adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2	Phase 3
AD5 Vectored COVID19 Vaccine	CanSino Biological Inc. & Beijing Institute of Biotechnology	E1/partially E3-deleted, replication-defective human adenovirus 5 (Ad5) vector (Ad5-N-V) expressing the SARS-CoV N protein	Phase 2
LNP encapsulated vaccine	Moderna & National Institute of Allergy and Infectious Diseases	mRNA-1273 lipid nanoparticle encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2	Phase 2
INO-4800	Inovio Pharmaceuticals & International Vaccine Institute	Plasmid pGX9501, encoding for the full length of the Spike glycoprotein of SARS-CoV-2 is administered through electroporation (Celectra device)	Phase 2
AG0301-COVID19	Osaka University AnGes Takara Bio	DNA vaccine encoding antigens from SARS-CoV-2	Phase 2
ZyCov-D Vaccine	Cadila Health Care Ltd	DNA vaccine encoding antigens from SARS-CoV-2	Phase 1 / 2
Inactivated Vaccine	Wuhan Institute of Biological Products & Sinopharm	Inactivated SARS CoV 2 strain	Phase 1 / 2
Covaxin	Bharat Biotech	Inactivated Whole-Virion	Phase 1 / 2
NVX CoV2373	Novavax	Full length recombinant SARS CoV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M	Phase 1 / 2
BNT162b1 and BNT162b2	BioNTech/Fosun Pharma/Pfizer	Nucleoside modified RNAs are formulated in lipid nanoparticles. BNT162b1 encodes a SARS-CoV-2 receptor-binding domain (RBD) antigen, while BNT162b2 encodes the virus’ full-length spike protein antigen.	Phase 1 / 2
GX-19	Genexine	DNA vaccine expressing SARS-CoV-2 S-protein antigen.	Phase 1 / 2
Inactivated Vaccine	Chinese Academy of Medical Sciences (IMBCAMS) & Yunnan Center for Disease Control and Prevention.	Inactivated SARS CoV 2	Phase 2
Gam-COVID-Vac Lyo.	Gamaleya Institute	Adenoviral-based vaccine against SARS-CoV-2	Phase 2
Protein subunit vaccine	Clover Biopharmaceuticals, GSK and Dynavax Technologies	S-Trimer protein that resembles the coronavirus spike protein	Phase 1
Protein Subunit vaccine	Institute of Microbiology, Chinese Academy of Sciences & Zhifei Longcom	Chinese Hamster Ovary cells producing a modified form of the coronavirus spike protein Adjuvanted recombinant protein (RBD-Dimer).	Phase 1
Covax19	Vaxine Pty & MedyTox	Spike protein along with an adjuvant called Advax	Phase 1
Protein Subunit	University of Queensland, GSK and Dynavax Technologies	Molecular clamp” technology containing stabilized Spike protein	Phase 1
COVAC1	Imperial College London	LNP containig a self-amplifying ribonucleic acid (saRNA) vaccine	Phase 1
CVnCoV	Curevac	mRNA encoding the spike protein of SARS-CoV-2 packaged into lipid nanoparticles.	Phase 1
ARCoV	People's Liberation Army (PLA) Academy of Military Sciences, Suzhou Abogen Biosciences and Walvax Biotechnology	SARS CoV 2 mRNA Vaccine	Phase 1
VLP vaccine	Medicago Inc, GSK and Dynavax	Plant derived virus like particles	Phase 1

References:

1. Weiskopf et al. Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients with acute respiratory distress syndrome. Link

2. Yarmarkovich et al. Identification of SARS-CoV-2 Vaccine Epitopes Predicted to Induce Long-Term Population-Scale Immunity. Link

3. Chen et al. The SARS-CoV-2 Vaccine Pipeline: an Overview. Curr Trop Med Rep. 2020 Mar 3;1-4. Link