Key Potential and Challenges of COVID-19 Intranasal Vaccines

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In a recent World Health Organization (WHO) livestream event, Chief Scientist Dr. Soumya Swaminathan shared with journalists on the logistical and therapeutic benefits of second-generation COVID-19 vaccines. One such promising type is the intranasal vaccine.

These vaccines, which are still under development, can be delivered through the nostrils, applied directly to the most likely route of infection and transmission. Intranasal drug delivery comes with the promises of better efficacy through stimulating local mucosal response, needle-free delivery, and is potentially self-administrable. These qualities make it very attractive to increase vaccine uptake and vaccine equity.

Diagram 1: Share of the population fully vaccinated against COVID-19, showing vaccine inequity in parts of Asia and Africa from Our World in Data.

Let us examine the key developments and how intranasal vaccines are expected to play an important role in the battle against COVID-19.

Vaccination rates in parts of Asia and Africa are still surprisingly low, particularly in developing markets and in rural areas. The lack of trained medical personnel and cold-chain capabilities are the two main barriers that can be solved by such an intranasal vaccine.

Multiple intranasal vaccine trials are already underway across the Asia Pacific. Examples include in China where Beijing Wantai is planning extensive trials for a nasal spray COVID-19 vaccine candidate while in Japan, the COVID-19 nasal spray vaccine is set to enter clinical trials.

The National Taiwan University-developed COVID-19 nasal spray vaccine is expected to soon enter human trials in Taiwan. Likewise, Thailand has also announced plans to start human trials on COVID-19 shots through a nasal spray.

Over in Australia, they are finding that delivering these vaccines as a nasal spray may work better for the population. Taking it even further, a South Korean bio firm claims that usage of face masks would not be required anymore with its nasal spray vaccine.

Vaccines injected intramuscularly are designed to produce a high immunoglobin G response in the bloodstream. This strong antibody response is the line of defense that vaccinated individuals carry towards the coronavirus.

Whereas, pre-clinical and clinical studies have shown that intranasal immunization elicits instead a mucosal immunoglobin A response, which is an antibody within the mucous membrane.

Diagram 2. The mechanisms for intranasal spray (top) and intranasal vaccines (bottom) from ScienceDirect.

Mucosal immune responses are most efficiently induced by vaccine exposure to mucosal surfaces, such as the nostril. This response has two primary benefits:

Reduced viral transmission through mucosal surfaces, which is the primary pathway for human-to-human transmission
Recruitment of tissue-resident, long-term memory B and T cells to the nasal passages, and respiratory tract

The University of Alabama, Birmingham’s immunologists Lund and Randall write in Science: “The ideal vaccination strategy, may use an intramuscular vaccine to elicit a long-lived systemic immunoglobulin G response and a broad repertoire of central memory B and T cells, followed by an intranasal booster…”

Ongoing studies in immunophenotyping analysis and cellular analysis of these mucosal immune responses are therefore underway, as intranasal vaccines can potentially provide increased long-term protection and reduced COVID-19 transmission rates through mucosal protection.

The main challenge of intranasal vaccines will come from the formulation, as intramuscular vaccine biologics are repurposed for a rough landing approach. Challenges include the increased dosage required, the necessity of adjuvants to stimulate immunogenicity, restricted delivery volume in the nasal cavity, and bodily defense mechanisms such as the mucociliary clearance on the permeability of drugs. The key factors affecting nasal absorption include physiological and physiochemical properties.

1. Physiological factors of the nose such as:

Mucosal permeability
Secretion of nasal mucosa enzymes and mucus
pH values, which can vary widely depending on the individual, time of day, and happenstance

2. Physiochemical properties of the vaccine formulation such as:

Concentration, dosage, and volume
Droplet size
pH level
Pharmaceutical dosage form
Excipients

Solid formats for nasal vaccines offer more stability than liquid formulations but may be more expensive in terms of cost and ease of administration. Additionally, carrier systems such as liposomes and virus-like particles may help the delivery of vaccine products.

To achieve success, intranasal vaccines must have remarkedly stable formulations made from precise control of physical properties, most notably droplet size, rheology, dosage uniformity, spray pattern, plume geometry, and in the interaction and characterization of its APIs and excipients.

Achieving international vaccine equity targets will substantially increase population immunity globally, protect health systems, enable economies to fully restart, and reduce the risk of new variants emerging.

DKSH provides physical, chemical, and biological characterization tools for drugs and drug formulations in the Asia Pacific. To learn more about the suite of products available, read more at Lab Solutions by DKSH.

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