New Nasal Delivery Strategy Shows Promise of Better HIV, COVID-19 Vaccines

Scientists have found a new approach that enables the effective delivery of vaccines via mucosal routes. This strategy promises better protection against the human immunodeficiency virus (HIV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is to blame for COVID-19.

Nasal Spray

Nasal Spray

People typically contract HIV through the genitals or anal mucosa while SARS-CoV-2 infections occur through the nasal mucosal. Many other viruses infect people through mucosal tissue – these include pathogens that cause flu, polio, and measles.

Read Also: French Researchers Develop a Nasal Vaccine That Can Block Transmission and Is Effective against All Variants of SARS-CoV-2

In essence, most virus infections occur via mucosal cells. Most vaccines against viral infections are given intramuscularly, however. This disparity plays a part to cause vaccines to not be at their potent best.

The intranasal approach proposed in this new research, therefore, promises a more effective way of promoting strong systemic immunity against many infectious viruses.

“To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry,” wrote the researchers.

The new method was reported in the journal Science Translational Medicine.

A delivery challenge

Scientists knew that both mucosal and systemic immune responses are needed for the most efficient defense against many pathogens. Intranasal vaccination can help greatly in shoring up mucosal immunity. However, there is a major hurdle with getting vaccines through the mucus and epithelial lining.

Nasal vaccines find it hard to access and trigger immune cells. This is because they are typically cleared out or broken down by mucus in the nose.

Albumin, in particular, makes it hard for vaccine components to reach underlying tissues. Researchers in this study wrote that this blood protein is “constitutively transcytosed bidirectionally across the airway epithelium.”

Read Also: Scientists Confirm Inhaled Vaccines More Effective For COVID-19 Than Nasal Sprays

Brittany Hartwell of the Massachusetts Institute of Technology and her fellow researchers were well aware of this challenge. They also knew that intranasal vaccination can produce more potent and protective immune responses, compared to intramuscular vaccination. So they set out to develop a new approach that could sidestep this challenge.

Novel vaccination method

The research team found a means of getting vaccine components, especially protein antigens, across mucosal barriers. This approach called the amph-protein strategy enables protein antigens to bind onto albumin to traverse mucosal surfaces.

These amph-proteins feature viral proteins that are joined to an amphiphilic tail, which binds albumin and interacts with the neonatal Fc receptor (FcRn).

Also referred to as the Brambell receptor, the FcRn safeguards the antibody immunoglobulin G (IgG) and albumin from being broken down. It also helps to get IgG across epithelial cells.

Hartwell and her colleagues found that the experimental intranasal strategy produced powerful systemic immunity against both HIV and SARS-CoV-2 in animal models.

Amph-proteins formulated with HIV Env gp120 protein or SARS-CoV-2 receptor-binding domain proteins set off robust antibody responses. These were observed in both the serum and nasal mucosa of mice and nonhuman primates that were vaccinated with them.

“Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein,” wrote Hartwell.

Read Also: Insulin Nasal Spray Improves Gait and Cognitive Function in Elderly Patients

Immunoglobulin A (IgA) and IgG help to induce systemic and mucosal immune responses against a wide variety of pathogens.

Receptor-binding domain immunization produced high levels of neutralizing antibodies in nasal washes, serum, and bronchoalveolar lavage of mice. Researchers also observed that intranasal amph-protein vaccination in rhesus macaques triggered 10-time higher antigen-specific IgG and IgA responses in both the serum and nasal mucosa, compared to when unmodified protein was used.

The researchers noted that amph-protein vaccines show impressive potential in effectively carrying antigens across mucosal barriers, based on their findings. Their approach could aid in boosting mucosal immunity against the dreaded viruses HIV and SARS-CoV-2, they wrote. With time, the strategy may be applied to developing vaccines against other infectious diseases.

References

Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity

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