Nasal Spray Protection Against COVID-19 and Influenza: A Breakthrough in Respiratory Infection Prevention

Major News Emerges in the Booming Field of Nasal Spray Protection!

Recently, a study published in Advanced Materials revealed that a novel nasal spray holds promise for blocking multiple airborne or droplet-transmitted infectious pathogens, including SARS-CoV-2 and influenza A virus. This is undoubtedly welcome news for the general public, who have been plagued by respiratory infectious diseases such as COVID-19 and influenza in recent years.

This is merely the tip of the iceberg regarding the rapid recent advancements in nasal spray protective products. In humanity’s fight against respiratory infectious diseases, these newly emerging nasal spray prophylactics are poised to play an increasingly vital role in the future.

This highly anticipated study was conducted by a research team from Brigham and Women’s Hospital, Harvard University. In this study, the team employed a pathogen-capturing and neutralizing nasal spray called Profi (PCANS), which demonstrated exceptionally prominent protective efficacy in preclinical studies.

Studies have shown that in a mouse model of severe influenza A, a single pre-exposure dose of Profi reduced lung viral titers by more than 99.99% in mice exposed to 25 times the lethal dose of influenza A virus, while maintaining normal levels of pulmonary inflammatory cells and cytokines, ultimately ensuring a 100% survival rate. In contrast, the survival rate in the control group was 0%, with no mice surviving.

In laboratory assays and tests conducted on 3D-printed human nasal models, Profi successfully blocked and neutralized major respiratory pathogens, including SARS-CoV-2, influenza A virus, adenovirus, respiratory syncytial virus (RSV), Escherichia coli, and Klebsiella pneumoniae. According to research, its droplet-capturing capacity is twice that of mucus alone.

Meanwhile, Profi also exhibits a prolonged duration of action. Studies have shown that a single dose can remain in the murine nasal cavity for up to 8 hours, ensuring at least 4 hours of protective efficacy.

It is worth noting that Profi is formulated entirely from inactive ingredients. The so-called pharmaceutical inactive ingredients, also known as excipients, refer to the carriers and additives used in drug manufacturing and prescription compounding. These are substances generally included in pharmaceutical formulations, excluding active ingredients or prodrugs, that have undergone reasonable safety assessments.

According to the research team, Profi’s formulation was developed using ingredients from the FDA’s Inactive Ingredient Database, which have previously been used in approved nasal sprays or are included on the FDA’s Generally Recognized as Safe (GRAS) list. The mechanism by which Profi blocks pathogens is well understood: the nasal spray forms a gel-like matrix in the nasal cavity that captures respiratory droplets, thereby immobilizing and effectively neutralizing the pathogens.

In layman's terms, Profi acts as an "invisible mask" for the nasal cavity.

It is worth noting that, because Profi utilizes a formulation of inactive ingredients, it is exempt from the complex pre-market approval process required by the FDA for pharmaceuticals, thereby enabling rapid market entry. This was also the primary objective behind the research team’s initial decision to develop products using inactive ingredients. Several core members of the research team co-founded Akita Biosciences and launched Profi in October 2023, marketing it as a nasal hygiene cosmetic product.

The findings of this study also lay the foundation for subsequent further clinical trials, demonstrating the significant potential of nasal protection products.

Zhao Xin, head of Blue Sail Medical’s Lanjushi brand, told VCBeat that the study demonstrates how interdisciplinary collaboration can combine materials science with medicine to develop innovative solutions capable of combating viral and bacterial respiratory infections. “This represents a trend toward adopting multidisciplinary, multi-perspective approaches to finding solutions in response to global health threats, thereby enhancing public health security and protecting humans from respiratory pathogens.”

In fact, basic research on such nasal protective products has been ongoing for over a decade. Products under BHM (Birmingham Healthcare Materials, a UK-based biotechnology company) have adopted a similar technological approach. Xu Shizhe, CEO of BHM, explained to VCBeat that carrageenan, a natural substance extracted from red algae, exhibits specificity against certain viral proteins. It can significantly inhibit immunodeficiency viruses and retroviruses, thereby markedly reducing viral load. Its inhibitory efficacy has been validated by clinical trials worldwide for more than ten years. Based on these findings, there has long been a proposal to utilize it in the nasal cavity for protective purposes.

The COVID-19 pandemic has significantly accelerated the development of nasal spray-based protective products. With the advent of the post-pandemic era, various respiratory infectious diseases have emerged in succession, posing unpredictable challenges and creating a demand for more routine preventive measures. While wearing masks remains the optimal choice, their limitations in comfort reduce compliance and willingness to use them consistently.

Against this backdrop, nasal spray products designed to balance comfort and protection have rapidly gained traction in response to public demand, with multiple such products entering the market in a short period. Due to their functional similarity to face masks, they are vividly referred to as “liquid masks.” However, as nasal sprays cannot guarantee 100% protection, they cannot completely replace face masks but rather serve as a complementary measure.

It should be noted that nasal spray protective products come in various types. Although they ultimately achieve the same goal, their underlying mechanisms differ significantly. Overall, based on their mode of action, nasal spray protective products can be primarily categorized into physical barrier types and neutralizing types. Profi belongs to the physical barrier category, functioning mainly by forming a physical film that blocks pathogens from invading the respiratory system through adsorption.

In addition to adsorption, physical barrier products employ another mechanism of action: killing or inhibiting pathogens through specific physical components. Nitric oxide (NO), backed by decades of pharmacological, toxicological, and safety research, has been proven to possess antimicrobial properties that can directly kill upper respiratory tract viruses, thereby preventing viral proliferation and spread to the lungs.

In 2021, SaNOtize, a Canadian biotechnology company, launched NONS (Nitric Oxide Nasal Spray), with nitric oxide as its primary active ingredient, for the treatment of COVID-19. Clinical studies have demonstrated that COVID-19 patients treated with NONS achieved a reduction in SARS-CoV-2 RNA viral load of over 95% within 24 hours and more than 99% within 72 hours.

Neutralizing agents represent another category of nasal spray protective products. Their core mechanism involves acting directly on the pathogen itself, preemptively binding to pathogens (such as the novel coronavirus) to disable their ability to invade the human body. There are several technological approaches for neutralizing agents, primarily including small-molecule peptides and large-molecule antibodies (such as nanobodies and IgM antibodies). Currently, products launched by several domestic pharmaceutical companies all adopt the neutralization approach.

Indicators of Several Commercially Available Nasal Spray Protective Products

Each of the two product categories has its own merits and offers a certain degree of protective efficacy. Relatively speaking, neutralization-based nasal spray products are developed primarily against specific pathogens, demonstrating potent neutralizing effects against target pathogens but lacking such activity against non-target pathogens. Furthermore, there is a risk of reduced efficacy in the event of viral mutations.

Among these, products developed via the peptide pathway may theoretically possess a certain degree of broad-spectrum activity, as they target different regions of the virus. Taking peptide-based products against SARS-CoV-2 as an example, they primarily act on the HR1 region of the viral spike protein. This region is relatively conserved across viral variants, suggesting that such products may theoretically exhibit greater efficacy against mutated strains.

Based on their mechanism of action, physical barrier products demonstrate a clear advantage in broad-spectrum efficacy, generally providing protection against a wide range of pathogens and, in theory, remaining effective even against previously unidentified pathogens. Furthermore, as they induce minimal changes to the nasal environment, physical barrier products exhibit superior persistence within the nasal cavity.

Xu Shizhe stated, “The expulsion of foreign bodies is an innate function of the nasal cavity. For nasal spray blockers to achieve optimal efficacy, the primary technical challenge lies in ensuring prolonged residence time on the nasal mucosa without altering the nasal environment. This is precisely the key focus in the development of physical barrier products. Currently, BHM has demonstrated a retention time of six hours in real-world conditions, based on data obtained from clinical tests conducted on volunteers’ nasal cavities.”

“In fact, carrageenan has been used globally for over a decade. However, BHM’s patented formulation incorporates gellan gum to prolong the residence time of carrageenan in the nasal cavity and enhance its physical barrier effect. We have just completed a study on the importance of gellan gum in nasal spray barriers. Our research found that gellan gum exhibits superior binding affinity with the nasal mucosa, allowing it to remain in the nasal cavity for a longer duration. These findings will be publicly released shortly,” he added.

Furthermore, as a safe, non-pharmacological, and non-specific technological platform, this technology can also serve as a drug delivery vehicle. Through collaborative research and development with pharmaceutical companies, it integrates active pharmaceutical ingredients with the carrier, enabling sustained and stable coverage at the site of administration to ensure long-term, precise drug release.

“Of course, regardless of the approach, timely testing against currently prevalent pathogens is essential. Zhao Xin noted that, taking the novel coronavirus as an example, whenever a new variant emerges, it is advisable for all brands to conduct relevant tests promptly to ensure effective neutralization of the new virus. It was reported that Blue Sail Medical has carried out timely testing and evaluation against multiple waves of predominant SARS-CoV-2 variants and their sublineages circulating in China, demonstrating that its products exhibit significant inhibitory effects against these strains.”

As a product category that has rapidly emerged in recent years, nasal spray protective products also face many of the challenges common to innovative offerings. Industry experts, in discussions with VCBeat, uniformly noted that due to their relatively short history, there are currently no clear regulatory guidelines for such products. This absence poses certain difficulties for product development and market promotion.

Xu Shizhe stated that although both physical and neutralizing products are externally formulated as nasal sprays, their differing internal mechanisms place them in distinct categories. Theoretically, once a product’s claimed efficacy reaches a level requiring regulatory oversight, physical products that rely solely on physical barrier mechanisms should be classified as medical devices globally. In contrast, neutralizing products, due to their pharmacological effects, should be classified as pharmaceuticals or combination drug-device products.

“Our product is new to the Chinese market, so it requires classification determination and clinical trials before launch, which takes a considerable amount of time. However, based on our classification assessment, the nasal spray blocker works through physical barrier mechanisms without producing any pharmacological effects, thus qualifying as a medical device, consistent with international standards. We are currently preparing for clinical registration in China as a Class II medical device, which will enable domestic production and reduce costs,” he explained to VCBeat.

Zhao Xin also stated that nasal spray-based blocking products constitute an entirely new industry, for which there are currently no specific implementation standards or regulatory guidelines in China. The industry is currently navigating uncharted territory, with expectations that it will become increasingly standardized over time. Blue Sail Medical is also actively working to promote the development of relevant standards.

Another challenge stems from clinical trials, which are particularly difficult for nasal spray products. Both the design of clinical trials and the achievement of their objectives are more challenging than those of conventional clinical trials. According to statistical data from a study, in the nearly ten years since the opening of registration on the Drug Clinical Trial Registration and Information Publicity Platform of the National Medical Products Administration (NMPA) until March 2023, only 80 registered clinical trials for nasal sprays were conducted in China, with over 70% of them registered after 2019.

Xu Shizhe stated that nasal sprays have faced considerable challenges since the animal testing phase: “First, there are significant differences between the nasal anatomy of animals and humans. Taking Profi’s research as an example, it was not feasible to conduct trials by exposing mice to pathogens via airborne transmission into their nasal cavities; instead, the pathogens were administered via intranasal instillation (drops). Similarly, Profi was also delivered via intranasal instillation rather than as a nasal spray in mice.”

“Even in human clinical trials, it is impossible to control all variables and ‘create’ the specific environment required for the study. Participants must continue their daily lives, exposed to diverse environments and lifestyle habits, which pose significant challenges to the clinical trial of the nasal spray and make achieving the expected results highly challenging,” he added.

However, the market waits for no one—spending several years to complete clinical trials before launching could very well mean missing the optimal window. During the COVID-19 pandemic, several Chinese pharmaceutical companies developed nasal spray products containing antibodies against the novel coronavirus for protective purposes, and these products subsequently entered clinical trial phases. However, VCBeat’s review of publicly available information reveals that there is little follow-up information on these related products.

Among them, Hybio Pharmaceutical explicitly announced in early 2024 that the Center for Drug Evaluation (CDE) of the National Medical Products Administration had approved its Class 1.1 innovative drug, the broad-spectrum prophylactic HY3000 nasal spray, to enter Phase III clinical trials. It remains one of the few projects with official confirmation this year that clinical development is still ongoing.

It is easy to imagine that clinical trials for such products are quite challenging.

Consequently, most nasal spray protective products currently on the market are launched as consumer goods to avoid terminology that might trigger regulatory scrutiny. Meanwhile, clinical trials are being conducted in parallel. For instance, Hybio Pharmaceutical has already launched its general health product leveraging relevant patents: the Hanhu Fusion Inhibitory Peptide Protective Spray.

Nevertheless, this has not dampened the strong public demand for nasal spray protective products. A search on e-commerce platforms reveals that multiple nasal spray products priced between 100 and 300 yuan enjoy robust sales. Blue Sail Medical’s “Lan Jushi” has accumulated over 50,000 reviews on JD.com, with reported repeat purchase rates exceeding 60%.

This has further spurred R&D enthusiasm among relevant companies. BHM is currently developing a new formulation designed to more effectively block airborne allergens and prevent allergic rhinitis, with a potential launch by the end of next year. Blue Sail Medical is strategically aligning its product portfolio and planning around the upper respiratory tract system. It has already launched two products for rhinitis and is developing a new anti-influenza product, expected to be released by the end of this year.

In the post-pandemic era, the public is facing an increasingly complex situation; the threat of respiratory infectious diseases has not diminished with the end of the pandemic. On the contrary, they are posing a more frequent threat to public health in a manner akin to “boiling a frog in warm water.”

How can humanity adapt to coexistence? Perhaps the answer lies in transforming rigid epidemic prevention concepts, helping people of all ages block sources of infection and prevent contamination in a safer and more effective manner. Nasal spray protective products, an emerging category, are poised to become a powerful weapon in ending respiratory infectious diseases over time.

References:

Joseph J, Baby HM, Quintero JR, Kenney D, Mebratu YA, Bhatia E, Shah P, Swain K, Lee D, Kaur S, Li XL, Mwangi J, Snapper O, Nair R, Agus E, Ranganathan S, Kage J, Gao J, Luo JN, Yu A, Park D, Douam F, Tesfaigzi Y, Karp JM, Joshi N. Toward a Radically Simple Multi-Modal Nasal Spray for Preventing Respiratory Infections. Adv Mater. 2024 Sep 24:e2406348. doi: 10.1002/adma.202406348. Epub ahead of print. PMID: 39318086.

Darren Incorvaia, Fiercebiotech.com, Nasal spray neutralizes army of respiratory diseases and protects mice from deadly influenza

21st Century Business Herald: “Six Domestic Nasal Spray Drugs for COVID-19 Prevention Under Development: Who Will Cross the Finish Line First?”