Intranasal vaccine: An effective strategy against COVID transmission?

New Delhi: COVID-19 pandemic saw the development and approval of various COVID-19 vaccines. As the pandemic rages on vaccine developers have continued to innovate by developing variant-specific and more efficient vaccines to end the pandemic. Bharat Biotech developed ‘iNCOVACC’ an intranasal COVID vaccine despite the slow uptake of COVID vaccines globally due to the declining rate of infections across nations. The recent surge in COVID-19 infections across Japan, the US, the Republic of Korea, Brazil and China has once again brought back the focus on the need for effective and safe vaccines to curb the pandemic.

The vaccine is a recombinant replication-deficient adenovirus vectored vaccine with a pre-fusion-stabilized SARS-CoV-2 spike protein. This vaccine candidate was evaluated in phases I, II and III clinical trials with successful results. The vaccine has been specifically formulated to allow intranasal delivery through nasal drops. The nasal delivery system has been designed and developed to be cost-effective in low- and middle-income countries. The vaccine stimulates a broad immune response – neutralising IgG, mucosal IgA, and T-cell responses.

Intranasal vaccines vs conventional vaccines

One of the conventional ways of vaccination is intramuscular vaccines, which primarily induce systemic immunity (antibody production). In this, the injection technique and needle size both determine how deep any substance is injected. It is important to make sure that the needle reaches the muscle and that the vaccine does not seep into subcutaneous tissue. Healthcare professionals often hesitate to use long needles as it causes discomfort to patients, as the skeletal muscles have a poor supply of pain fibres as compared to skin and subcutaneous tissue.

Another way of vaccination is through oral shots. Here a combination of mucosal and parenteral administration of antigen is required. It induces both systemic and mucosal immunity and cell-mediated immunity by DNA vaccination. The acidic nature of the gastrointestinal tract, its low absorption and its bioavailability, do not provoke a sufficient antigen-specific immune response.

In contrast, for most microbes, the nasal mucosa is usually the first battleground that needs to be conquered. Nasal vaccination induces both mucosal (protection at the infection site) and systematic immunity. The nasal vaccine often provides immunity at other mucosal sites- gastrointestinal tract, respiratory tract, urogenital tract, and ocular cavities. Plus it is easily accessible and causes little discomfort to patients. In terms of handling, pharmacists and nurses can also perform mass vaccination.

How does the intranasal vaccine induce immunity?

According to the Lancet article titled ‘Intranasal COVID-19 vaccines: From bench to bed’, an intranasal vaccine is a promising preventive strategy for SARS-CoV-2 considering the remarkable protective immunity in the mucosal sites. SARS-CoV-2 is a typical mucosal pathogen that spreads from person to person via respiratory droplets. It infects human epithelial cells in the respiratory tract by binding to angiotensin-converting enzyme 2 (ACE2) receptors through the viral spike (S) receptor-binding domain (RBD). Mucosal immunity is essential for adequate and long-term protection against viral infection. When SARS-CoV-2 enters the nasal cavity, the respiratory epithelial layer becomes the first barrier against viral infection. Then, the innate immunity components in the upper airway mucosa become the first line of defence, which consist of diverse immune cells, including phagocytic neutrophils, macrophages, dendritic cells (DCs), natural killer cells, mast cells.

If the viruses reach deeper airways or lungs, pathogens-associated molecular patterns (PAMPs) expressed on viruses will be recognised by pattern recognition receptors (PRRs) expressed in respiratory epithelial cells, DCs, and alveolar macrophages. Endosomal enzymes degrade viral particles and release single-stranded RNA that can be recognised by toll-like receptor (TLR) 7 or TLR8. Activation of the PRRs leads to increased expression of proinflammatory cytokines such as type I interferon (IFN-I).

Mucosal immunisation can induce extensive adaptive immune responses, characterised by mucosal secretory IgA (sIgA) antibodies and resident memory T (TRM) cells.

How do intranasal vaccines prevent transmission?

Intranasal vaccines like iNCOVACC are administered as drops directly into the nose, where it triggers an immune response, blocking the infection and breaking the cycle of transmission. These mucosal vaccines target thin mucous membranes that line the nose, mouth and lungs. By prompting immune responses where SARS-CoV-2 first enters the body, mucosal vaccines could prevent even mild cases of illness and block transmission to other people. Till now, COVID-19 injectable vaccines have been unable to do so.

What other intranasal vaccines are in development or approved for rollout in the market?

Around 100 different intranasal COVID vaccines are under development worldwide, according to an analysis by health data firm Airfinity and Nature, with some 20 being tested on humans.

In 2022, one notable intranasal vaccine that was recently in development but failed to induce immunity was Astrazeneca’s ChAdOx1, which is an intranasal version of Astrazeneca’s and Serum Institute of India’s intramuscular injectable vaccine. The Russian health ministry also registered a nasal version of Sputnik V for COVID-19 in April 2022.

iNCOVACC rolled out as a booster dose

Bharat Biotech received approval last month from the Central Drugs Standard Control Organisation (CDSCO) for using iNCOVACC as a booster dose for those aged above 18 years. It is available on the CoWin platform and priced at Rs 800 for private markets and Rs 325 for the government. iNCOVACC is administered as a 2-dose series, four weeks apart. A total of eight drops (0.5 ml per dose), four drops in each nostril.