Intranasal immunizations are simple, easy, convenient, and safer than other routes of administration. Oral and Intramuscular vaccination has been considered till date as the ultimate ways, but nasal route offers advantages such as ease of self administration and induction of mucosal as well as systemic immunity. Both liquid and dry powder formulations can be given via intranasal route.

1. Intranasal Vaccine
Hira Nusrat
Mphil Scholar
Department of Zoology
University of Peshawar
Hiranusrat818@gmail.com
VETERINARY VACCINOLOGY

2. Intranasal Vaccination
Intranasal immunizations are simple, easy, convenient, and safer
than other routes of administration.
Oral and Intramuscular vaccination has been considered till date as
the ultimate ways, but nasal route offers advantages such as;
 ease of self administration and
 induction of mucosal as well as systemic immunity.
Both liquid and dry powder formulations can be given via intranasal
route.
Birkhoff M, Leitz M, Marx D. Advantages of Intranasal Vaccination and
Considerations on Device Selection. Indian J Pharm Sci. 2009 Nov-Dec;71(6):729–
31. PMCID: PMC2846493.

3. Importance of Intranasal
Vaccination
• The nasal route has excellent potential for vaccination due to
the organized immune systems of the nasal mucosa.
• Non-invasive, Needle-free.
• Ease of administration – does not require trained health care
workers.
• Elimination of needle-associated risks (injuries and
infections).
• High compliance (Ideally suits for children’s and adults).
• Scalable manufacturing – able to meet global demand.

4. Administration/Delivery of vaccines
A great consideration has to be given while selecting a suitable
device for nasal administration since the volume delivered is
very low. A number of devices are available based on number
of doses to be administered and type of dosage formulation.
The delivery system selection depends upon the antigen being
used for the proposed indication, patient type, and marketing
preferences. There are different options available to
deliver nasal vaccine such as;
• Drops,
• Powder,
• Aerosol sprays, and
• The application of nasal gel.

5. • Nasal drops or syringes:
Nasal drops are convenient and the most simple method for delivery
of nasal vaccines. The nasal drops are administered using a nasal
dropper or syringes. The major disadvantage of this system is the lack
of dose precision and difficulty for the pediatric population. Some
studies reported that nasal drops deposit human serum albumin in the
nostrils more efficiently than nasal sprays.
• Nasal powder
Nasal powder formulations are highly stable compared to liquid
formulations. Nasal powders can extend the residence time for powder
formulations on the nasal mucosa, potentially increasing the local and
systemic immune response. However, the production of nasal dry
powders is quite complicated with required particle size, particle
distribution, and performance characteristics when compared with other
dosage forms.
Administration/Delivery of vaccines

6. • Aerosol (The nasal spray is the most widely used device)
The aerosol route of delivery of vaccines is one of the most
preferred for nasal administration compared with other nasal
dosage forms and also less reactogenic than the subcutaneous route
of administration. Aerosol vaccination via the lungs targets an
epithelium critical to host defense against inhaled pathogens and
provides an exciting opportunity in the development of newer and
more effective tuberculosis (TB), measles, and influenza vaccines.
Administration/Delivery of vaccines

7. • Nasal gel
Nasal gels are generally used for colds, allergies, low humidity,
or overuse of decongestant. Nasal vaccine gels are a high-
viscosity solution or suspension in which antigenic molecules are
dispersed.
Special application techniques are required for the administration
of nasal gel vaccines because of their highly viscous formulation
and poor spreading abilities. Nasal gel is an alternative and
promising novel dosage delivery system to achieve the immune
response.
https://www.sciencedirect.com/book/9780323399814/micro-and-nanotechnology-in-
vaccine-development
Administration/Delivery of vaccines

8. Accordingly, the intranasal route may be used for vaccination
against infectious bovine rhinotracheitis or feline viral
rhinotracheitis.
When large numbers of animals are involved, methods other than
injection may be used.
In farmed fish, vaccination is an important method for
preventing infectious diseases. Depending on the nature of the
vaccine, injection into the abdominal cavity or immersion of fish
in a diluted solution of antigenic material may be used.
(Book: Concise Review of Veterinary Microbiology 2015 Second edition. By
P. J. Quinn, B. K. Markey, F. C. Leonard, E. S. Fitzpatrick, S. Fanning Wiley
Blackwell)
Administration/Delivery of vaccines

9. Factors affecting intranasal vaccines
Factors that influence the success of vaccination programmes in
animals include:
– The nature, composition and efficacy of the vaccine,
– The ages of the animal
– Population at time of vaccine administration,
– Routes of transmission of the infectious agents involved
and
– The methods used to administer the vaccine.
• In mammals, most vaccines are administered by injection.
• For diseases that affect particular systems, vaccines may be given by a
route that stimulates local immune responses at the usual site of
invasion.

10. ADVANTAGES OF INTRANASAL VACCINATION
• For most microbes, the nasal mucosa is the first barrier which
must be conquered. So it's not a surprise, that this mucosa is
very immune-competent. It was shown, that even small
amounts of antigen elicit a protective response.
• It is also a clear advantage, that nasal vaccination induces both
mucosal (protection at site of infection) and systemic
immunity. In contrast, intramuscular vaccination primarily
induces systemic immune response (antibody formation).
• In addition, intranasal vaccination may confer protection
against infections at other mucosal sites, such as the lungs,
intestines and genital tract, and provide cross-protection
against variant strains through mucosal antibody secretion.
• Another important advantage: the nasal cavity is easily
accessible.

11.  An intranasal vaccine stimulates a broad immune response –
 Neutralizing IgG, mucosal IgA, and
 T cell responses.
 Immune responses at the site of infection (in the nasal mucosa) – essential
for blocking both infection and transmission of microorganisms.
ADVANTAGES OF INTRANASAL VACCINATION

12. ADVANTAGES OF INTRANASAL VACCINATION
• Intranasal administration may be best suited for barrier
vaccinations, following the outbreak of highly infectious
diseases, because less skilled persons like pharmacists or nurses
can do mass vaccinations.
• Intranasal vaccines may be most beneficial for special
populations:
– children (easy to use, non-invasive)
– elderly patients (easy to use, non-invasive)
– HIV-infected patients (no fear for needle stick injuries)
– multi-morbid patients (fed up with injections)
Birkhoff M, Leitz M, Marx D. Advantages of Intranasal Vaccination and
Considerations on Device Selection. Indian J Pharm Sci. 2009 Nov-Dec;71(6):729–
31. PMCID: PMC2846493.

13. ADVANTAGES OF INTRANASAL VACCINATION
Intranasal vaccination can have several advantages over conventional
intramuscular vaccines, not least because they can generate strong
immune responses at key sites of pathogen exposure such as the lungs.
In Cell Reports, Diamond and colleagues use a chimpanzee adenoviral-
vectorized vaccine that expresses the CoV-2 spike protein (ChAd-
SARS-CoV-2-S) and investigate the durability, dose response and
cross-protective effects in humanized mice after intranasal
administration. A single intranasal dose of vaccine induced humoral
responses that were superior to the intramuscular route both in terms of
antibody titer and neutralizing efficacy. Intranasal vaccine also
generated long-lived plasma cells in the bone marrow that were absent
or minimally present with intramuscular dosing. Notably, intranasal
vaccination protected against variants of concern such as B.1.351
(Beta) for up to 9 months.
Fehervari, Z. Intranasal vaccination. Nat Immunol 22, 1071 (2021).
https://doi.org/10.1038/s41590-021-01016-x

14. • Recent studies indicate that IM vaccines are poor in
controlling viral replication and nasal shedding in the upper
respiratory tract, leading to asymptomatic or milder
symptomatic infection that can still transmit virus to others. In
contrast, IN vaccines have the potential to induce sterilizing
immunity against mucosal pathogens.
Hassan AO, Kafai NM, Dmitriev IP, et al. A single-dose intranasal ChAd vaccine protects
upper and lower respiratory tracts against SARS-CoV-2. Cell. 2020;183(1):169–184.e13.
ADVANTAGES OF INTRANASAL VACCINATION

15. Cell Reports 2021 36DOI: (10.1016/j.celrep.2021.109452)
Copyright © 2021 The Author(s) Terms and Conditions

16. Many of the side effects seen following intranasal administration are
caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial
nerve (trigeminus nerve) is responsible for sensing pain and irritation
following nasal administration but the 7th cranial nerve (facial nerve) will
respond to such irritation by stimulating glands and cause facial
expressions in the subject. The first cranial nerve (olfactory nerve),
however, is the target when direct absorption into the brain is the goal,
since this is the only site in our body where the central nervous system is
directly expressed on the mucosal surface. The nasal mucosa contains 7
cell types and 4 types of glands. Four types of cells and 2 types of glands
are located in the respiratory region but 6 cell types and 2 types of glands
are found in the olfactory region.
DISADVANTAGES OF INTRANASAL
VACCINATION
Sveinbjörn Gizurarson. Anatomical and Histological Factors Affecting Intranasal Drug
and Vaccine Delivery. Current Drug Delivery, 2012, 9, 566-582