A nasal vaccine for COVID-19 is administered through the nose, typically as a spray or drops, rather than by injection. This method aims to induce an immune response directly at the body’s initial entry points for the SARS-CoV-2 virus, such as the nose, mouth, and throat. The primary purpose of these vaccines is to offer an alternative to traditional injectable vaccines, potentially providing a different layer of protection against the virus.
How Nasal Vaccines Work
Nasal vaccines operate by stimulating mucosal immunity, a specialized defense system present in the mucous membranes lining various parts of the body, including the respiratory tract. When the vaccine is delivered into the nose, the antigens, components of the virus designed to provoke an immune response, are taken up by immune cells within the nasal lining and tonsils. This direct exposure differs from systemic immunity induced by injectable vaccines, which circulate antibodies throughout the bloodstream.
The stimulation of mucosal immunity leads to the production of secretory IgA (SIgA) antibodies. These antibodies are particularly abundant in mucosal secretions like those found in the nose, mouth, and throat. Targeting SARS-CoV-2, SIgA antibodies can neutralize the virus before it descends into the lungs and establishes a more severe infection. Research indicates that B cells activated in the nasal immune system produce SIgA in the nasal mucosa and also migrate to other areas to produce different types of antibodies, including IgG.
Why Nasal Vaccines are Being Developed
Nasal vaccines are being developed for several reasons, offering advantages over conventional injected vaccines. One significant benefit is their potential to block infection at the virus’s initial entry points. This localized immune response could reduce viral replication and shedding in the upper respiratory tract, limiting transmission to others. Traditional injectable vaccines are effective at preventing severe illness and death but do not consistently halt transmission.
Beyond their potential to reduce transmission, nasal vaccines offer practical administration advantages. They are needle-free, which can increase vaccine acceptance and compliance, especially for those with needle fear. The ease of administration could also simplify mass vaccination campaigns by reducing the need for trained medical personnel, potentially lowering administration costs and medical waste. They are also more accessible for broader public health initiatives.
Current Status of Nasal COVID Vaccines
Several nasal COVID-19 vaccines are in development and approval worldwide. In India, a nasal vaccine named iNCOVACC, developed by Bharat Biotech in collaboration with Washington University, received approval for restricted emergency use in adults over 18 in September 2022. This vaccine is a replication-deficient adenovirus vectored vaccine.
In the United States, a nasal vaccine from Washington University, licensed to Ocugen, received FDA approval in February 2025 to begin a Phase 1 clinical trial. This trial, funded by Project NextGen and NIAID, will enroll 80 adults to assess safety and immunogenicity, including antibody production. Other nasal vaccine candidates in various stages of clinical trials globally include Razi Cov Pars (Iran), Sputnik (Russia), and Convidicia (China).
Obstacles in Nasal Vaccine Development
Developing effective nasal vaccines presents several challenges. A primary hurdle is achieving a robust and durable immune response within the nasal passages. The nasal cavity’s structure, including cilia and mucus, can hinder antigen uptake and clearance, affecting vaccine stability and protective immunity. The limited volume feasible for nasal administration also restricts the amount of antigen that can be delivered.
Formulation stability is another challenge, as nasal vaccines can be developed as liquids or powders, each with specific potency requirements. Ensuring the vaccine remains stable and effective within the nasal environment, with varying pH levels and enzymatic activity, requires careful design. Optimizing the delivery system, such as nasal spray pumps or powder technologies, is important to ensure the vaccine reaches the appropriate areas for optimal immune stimulation. Regulatory pathways for these novel delivery methods also add complexity to development and approval.