Oral and nasal vaccination: current prospects, challenges, and impact of nanotechnology-based delivery systems

Paiva, Natália Floriano; Vicentini, Fabiana Testa Moura de Carvalho

doi:10.1590/s2175-97902023e21769

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Article • Braz. J. Pharm. Sci. 59 • 2023 • https://doi.org/10.1590/s2175-97902023e21769 copy

Oral and nasal vaccination: current prospects, challenges, and impact of nanotechnology-based delivery systems

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Currently, mucosal vaccine administration has stood out as an easier and non-invasive application method. It can also be used to induce local and systemic immune responses. In the COVID-19 pandemic context, nasal and oral vaccines have been developed based on different technological platforms. This review addressed relevant aspects of mucosal vaccine administration, with emphasis on oral and nasal vaccinations, in addition to the importance of using nanotechnology-based delivery systems to enable these strategies.

Keywords:
Mucosal vaccination; Oral vaccine; Nasal vaccine; Nanocarriers; Nano-vaccinology

Vaccine platform	Type of vaccine	Number of doses	Route of administration	Phase	Developers
Live attenuated virus	MV-014-212 A live attenuated vaccine that expresses the spike protein of SARS-CoV-2	1	Intranasal	Phase 1	Meissa Vaccines, Inc.
Live attenuated virus	COVI-VAC	1-2	Intranasal	Phase 3	Codagenix and Serum Institute of India
Inactivated virus	CoronaVac Inactivated SARSCoV-2 vaccine	2	Intramuscular	Phase 4	Sinovac Research and Development Co., Ltd
Inactivated virus	Inactivated SARSCoV-2 vaccine (Vero cell)	2	Intramuscular	Phase 4	Sinopharm, China National Biotec Group Co and Wuhan Institute of Biological Products
Protein subunit	CoV2-OGEN1, protein based vaccine	1-2	Oral	Phase 1	USSF/Vaxform
Protein subunit	RBD + AgnHB	3	Intranasal	Phase 1/2	Center for Genetic Engineering and Biotechnology (CIGB)
Protein subunit	Full length recombinant SARSCoV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M	2	Intramuscular	Phase 3	Novavax
Protein subunit	MVC-COV1901 (Spike-2P protein + adjuvant CpG 1018) MVC-COV1901 (Beta)	2	Intramuscular	Phase 4	Medigen Vaccine Biologics, Dynavax and National Institute of Allergy and Infectious Diseases (NIAID)
Virus like particle	Receptor Binding Domain (RBD) SARS-CoV-2 HbsAg VLP vaccine	2	Intramuscular	Phase 1/2	Serum Institute of India, Accelagen Pty and SpyBiotech
Virus like particle	Coronavirus-like particle COVID-19 (CoVLP)	2	Intramuscular	Phase 3	Medicago Inc.
RNA based vaccine	Comirnaty BNT162b2 (3 LNP - mRNAs)	2	Intramuscular	Phase 4	Pfizer/BioNTech and Fosun Pharma
RNA based vaccine	mRNA-1273 Spikevax	2	Intramuscular	Phase 4	Moderna and National Institute of Allergy and Infectious Diseases (NIAID)
DNA based vaccine	BacTLR-Spike oral DNA vaccine	1	Oral	Phase 1	Symvivo Corporation
DNA based vaccine	AG0301-COVID19	2	Intramuscular	Phase 2/3	AnGes, Takara Bio and Osaka University
DNA based vaccine	INO-4800 + eletroporation	2	Intradermal	Phase 3	Inovio Pharmaceuticals, International Vaccine Institute and Advaccine (Suzhou)
Viral vector (replicating)	rVSV-SARS-CoV-2-S vaccine	1	Intramuscular	Phase 2/3	Israel Institute for Biological Research
Viral vector (replicating)	Intranasal flubased-RBD	2	Intranasal	Phase 3	University of Hong Kong, Xiamen University and Beijing Wantai Biological Pharmacy
Viral vector (nonreplicating)	PIV5 vector that encodes the SARSCoV-2 spike protein	1	Intranasal	Phase 1	CyanVac LLC
Viral vector (nonreplicating)	VXA-CoV2-1 Ad5 adjuvanted oral vaccine platform	2	Oral	Phase 2	Vaxart
Viral vector (nonreplicating)	BBV154, Adenoviral vector COVID-19 vaccine	1	Intranasal	Phase 3	Bharat Biotech International Limited
Viral vector (nonreplicating)	Covishield ChAdOx1-S (AZD1222)	1-2	Intramuscular	Phase 4	AstraZeneca and University of Oxford
Viral vector (non-replicating)	Ad26.COV2.S	1-2	Intramuscular	Phase 4	Janssen Pharmaceutical Johnson & Johnson
Viral vector (non-replicating)	Recombinant novel coronavirus vaccine (Adenovirus type 5 vector)	1	Intramuscular	Phase 4	CanSino Biological Inc./Beijing Institute of Biotechnology

Route of administration	Advantages	Disadvantages
Oral and Intranasal	Possibility of self-administration	Requires higher doses than those used in the parenteral route
	Induction of mucosal immune response
	Non-invasive and painless method
	Applicable for mass vaccination
Oral		Mucosal coating is a barrier to absorption of macromolecules
	Ease of administration and increased adherence	Secretion of antimicrobial compounds occurs within the mucous membrane
	Large-scale production with low costs	Gastric degradation due to low stomach pH, presence of bile salts and enzymes
	High absorptive capacity of the intestinal epithelium	First pass metabolism
	Presence of constituent lymphoid tissue	Intestinal motility and gastric emptying
		Inaccurate dosage and reduced bioavailability
Intranasal	Large mucosal surface area, porous endothelial membrane and high vascularization of the epithelium
	Presence of lymphoid tissue associated with the nasopharynx	Epithelial cell layer forms a barrier to absorption
	Induction of the immune response in mucous membranes further away from the nasal cavity	Fast mucociliary clearance and short residence time
	Protection against pathogens that enter the respiratory tract	Reduced delivery volume due to low nasal cavity capacity
	Prevents the spread of the pathogen through the air	Nasal Obstruction is an important obstacle
	Reduced activity of degradation enzymes and avoids 1st pass metabolism

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: F. T. M. de C. Vicentini. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Universidade de São Paulo. Av. Café S/N, Monte Alegre, Ribeirão Preto, São Paulo, Brasil. 14040-903, Ribeirão Preto, SP. Phone/Fax: 00 55 16 33154257 / 33154232. E-mail: fabtesta@fcfrp.usp.br.