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Particulate vaccines can be administered as either oral solutions or in sublingual or buccal film dosage forms. Besides improved patient compliance, the major advantage of oral, sublingual, and buccal routes of administration is that they can elicit mucosal immunity. Mucosal immunity, along with systemic immunity, can be a strong defense against SARS-CoV-2 as the virus enters the system through inhalation or saliva.
Particulate COVID vaccine is a vaccine that can be developed by using nano- or microparticles as platforms. Particles consist of an active principle (drug or biologically active material) that is dissolved, entrapped, or encapsulated [1]. Microparticles and nanoparticles can be utilized as drug carriers into which drugs or antigens may be incorporated in the form of solid solutions or solid dispersions. Nano- or microparticles have been shown to enhance the delivery of certain drugs across several natural and artificial membranes. Although the currently marketed mRNA vaccines are in particulate form, these are administered via the intramuscular route. This route of administration is at a disadvantage due to decreased patient compliance associated with injections. Therefore, particulate vaccines that can be administered by some other, painless route such as buccal or sublingual can be a better option for this vaccine. In this article, we will review some of the current COVID-19 vaccine platforms and discuss their limitations. We will further explore the feasibility of developing a COVID vaccine that can be administered orally, sublingually or via the buccal route by utilizing nano- or microparticles as a platform.
Vaccine Candidates | Classification of Vaccine | Clinical Phase | Lead Development Company/Collaboration |
---|---|---|---|
GRAd-COV2 | Adenovirus-based vaccine | Phase 1 | ReiThera; Leukocare; Univercells; Lazzaro Spallanzani National Institute for Infection |
ChAd-SARS-CoV-2-S | Adenovirus-based vaccine | Preclinical | Washington University School of Medicine in St. Louis |
LinealDNA | DNA Vaccine | Preclinical | Takis Biotech |
AG0301-COVID19 | DNA vaccine | Phase 1/2 | AnGes, Inc. |
GX-19 | DNA vaccine | Phase 1/2 | Genexine |
INO-4800 | DNA vaccine (plasmid) |
Phase 1/2 | Inovio Pharmaceuticals; Center for Pharmaceutical Research, Kansas City. Mo.; University of Pennsylvania, Philadelphia |
ZyCoV-D | DNA vaccine (plasmid) |
Phase 2 | Zydus Cadila |
AAVCOVID | Gene-based vaccine | Preclinical | Massachusetts General Hospital; University of Pennsylvania |
No name given | gp96-based vaccine | Preclinical | Heat Biologics; University of Miami Miller School of Medicine |
No name given | Ii-Key peptide COVID-19 vaccine | Preclinical | Generex Biotechnology |
No name given | Inactivated vaccine | Phase 1/2 | Research Institute for Biological Safety Problems, Rep of Kazakhstan |
No name given | Inactivated vaccine | Phase 3 | Wuhan Institute of Biological Products; China National Pharmaceutical Group (Sinopharm); Henan Provincial Center for Disease Control and Prevention |
Covaxin | Inactivated vaccine | Phase 2 | Bharat Biotech; National Institute of Virology |
No name given | Inactivated vaccine | Phase 1/2 | Chinese Academy of Medical Sciences, Institute of Medical Biology; West China Second University Hospital, Yunnan Center for Disease Control and Prevention |
No name given | Inactivated vaccine | Preclinical | Shenzhen Kangtai Biological Products |
BBIBP-CorV | Inactivated vaccine | Phase 3 | Beijing Institute of Biological Products; China National Pharmaceutical Group (Sinopharm); Henan Provincial Center for Disease Control and Prevention |
CoronaVac | Inactivated vaccine (formalin with alum adjuvant) | Phase 3 | Sinovac; Sinovac Research and Development Co., Ltd. |
AdCOVID | Intranasal vaccine | Preclinical | Altimmune; University of Alabama at Birmingham |
T-COVIDTM | Intranasal vaccine | Preclinical | Altimmune |
Bacillus Calmette-Guerin (BCG) vaccine | Live-attenuated vaccine | Phase 2/3 | University of Melbourne and Murdoch Children’s Research Institute; Radboud University Medical Center; Faustman Lab at Massachusetts General Hospital |
V591 | Replicating viral vector | Phase 1 | University of Pittsburgh’s Center for Vaccine Research; Themis Biosciences; Institut Pasteur |
bacTRL-Spike | Monovalent oral vaccine (bifidobacteria) | Preclinical | Symvivo |
COVAX-19 | Protein subunit Monovalent spike protein vaccine |
Phase 1 | Vaxine Pty Ltd.; Royal Adelaide Hospital |
No name announced | mRNA lipid nanoparticle | Early research | CanSino Biologics, Precision NanoSystems |
mRNA-1273 | LNP-encapsulated mRNA vaccine | Phase 3 | Moderna; Kaiser Permanente Washington Health Research Institute |
BNT162 | 3 LNP-mRNAs-based vaccine | Phase 3 | Pfizer, BioNTech |
CVnCoV | mRNA-based vaccine | Phase 1 | CureVac |
No name given | mRNA-based vaccine | Preclinical | Chulalongkorn University’s Center of Excellence in Vaccine Research and Development |
UB-612 | Multitope peptide-based vaccine | Phase 1 | COVAXX; United Biomedical Inc. (UBI) |
JNJ-78436735 | Non-replicating viral vector | Phase 3 | Johnson & Johnson |
Sputnik V COVID-Vac; Гам-КОВИД-Вак20 |
Non-replicating viral vector Adenovirus-based vaccine |
Phase 3 | Gamaleya Research Institute, Acellena Contract Drug Research and Development |
EpiVacCorona | Peptide vaccine | Phase 1/2 | Federal Budgetary Research Institution State Research Center of Virology and Biotechnology |
No name given | Plant-based adjuvant vaccine | Phase 1 | Medicago; GSK; Dynavax |
No name given | Protein subunit vaccine S protein20 |
Phase 1/2 | Sanofi; GlaxoSmithKline |
No name given | Protein subunit RBD-based vaccine |
Phase 1/2 | Kentucky Bioprocessing, Inc. |
AdimrSC-2f | Protein subunit vaccine | Phase 1 | Adimmune |
No name given | Protein subunit vaccine | Phase 1 | CSL; The University of Queensland; Seqirus |
SCB-2019 | Protein subunit vaccine | Phase 1 | GlaxoSmithKline, Sanofi, Clover Biopharmaceuticals, Dynavax and Xiamen Innovax; Linear Clinical Research (Australia) |
No name given | Protein subunit vaccine | Preclinical | University of Saskatchewan Vaccine and Infectious Disease Organization-International Vaccine Centre |
PittCoVacc | Recombinant protein subunit vaccine | Preclinical | UPMC/University of Pittsburgh School of Medicine |
RBD-Dimer (relief) |
Protein subunit Adjuvanted recombinant protein |
Phase 2 | Anhui Zhifei Longcom Biopharmaceutical, Institute of Microbiology of the Chinese Academy of Sciences |
No name given | Recombinant vaccine | Preclinical | Sanofi, Translate Bio |
Ad5-nCoV | Recombinant vaccine (adenovirus type 5 vector) | Phase 3 | CanSino Biologics; Tongji Hospital |
VXA-CoV2-1 | Recombinant vaccine (adenovirus vector) | Phase 1 | Vaxart |
V590 | Recombinant vaccine (stomatitis virus) | Phase 1 | Merck; IAVI |
DelNS1-2019-nCoV-RBD-OPT1 | Replicating viral vector | Phase 1 | Xiamen University, Beijing Wantai Biological Pharmacy; Jiangsu Provincial Centre for Disease Control and Prevention |
No name announced | Replicating viral vector | Preclinical | Federal Budgetary Research Institution (FBRI); State research center of virology and biotechnology “VECTOR” |
AZD1222 ChAdOx1-S20 |
Non-Replicating viral vector vaccine | Phase 3 | The University of Oxford; AstraZeneca; IQVIA; Serum Institute of India |
HDT-301 | RNA vaccine | Preclinical | University of Washington; National Institutes of Health Rocky Mountain Laboratories; HDT Bio Corp. |
LNP-CoVsaRNA | Self-amplifying RNA vaccine | Phase 1/2 | Imperial College London |
HaloVax | Self-assembling vaccine | Preclinical | Voltron Therapeutics, Inc.; Hoth Therapeutics, Inc.; MGH Vaccine and Immunotherapy Center |
LUNAR-COV19 [38] | Self-replicating RNA vaccine | Phase 1/2 | Arcturus Therapeutics and Duke-NUS Medical School |
CDX-005 [39][40] | Weakened | Phase 1 | Codagenix, Serum Institute of India |