Building Single Dose, Intranasal Vaccines to Prevent COVID-19 and RSV

In the second of four features on Meissa Vaccines, Big4Bio explores the company’s technology and pipeline.

Company to Watch – Meissa Vaccines

When Marty Moore, Meissa Vaccines’ cofounder and CEO, is asked about why the company is advancing an intranasal recombinant live attenuated vaccine for COVID-19, he talks about the oral polio vaccine.

Many remember Jonas Salk, who developed the inactivated polio vaccine, and Albert Sabin, who developed the oral, live attenuated polio vaccine. Salk got there first with the inactivated, injected vaccine, but Sabin’s live attenuated vaccine defeated polio globally.

“Live attenuated vaccines may take a little longer to develop,” says Moore, “but ultimately are end game vaccines because they are effective, generally low cost, and easy to administer globally, if they are given in a single dose without a needle, like Sabin’s vaccine. Most importantly, when fighting a respiratory virus like SARS-CoV-2 or RSV, they can be delivered intranasally to block infection and transmission.”

Meissa Vaccine’s CSO Roderick Tang and CEO Marty Moore review data with a Meissa scientist in the lab

Making vaccines from a live virus is a balancing act between safety and immunogenicity that, if successful, can promote broad immunity that mimics natural immunity against the infecting agent. However, this balancing act is not always easily obtained.

Historically, live attenuated vaccines, like oral polio, were made by weakening the replication or growth of the pathogen until it was safe enough to be a vaccine. This was done by serially passaging pathogens in culture to weaken their growth.

Pathogens have essential genes necessary for replication. Serial passage mutates these replication machinery genes, dials down replication, and attenuates growth, producing candidate vaccine strains. But there’s a catch. A weakened virus produces a weakened immune response, hence the balancing act.

Meissa Vaccines is taking a new approach to producing live attenuated vaccines for serious respiratory viruses like RSV. They are targeting the non-essential genes of RSV that govern virulence, the severity of disease. These RSV genes work by blocking the immune response.

Meissa’s approach is to attenuate the RSV genes that promote disease by blocking the immune response, rather than attenuating RSV genes that function in replication. The resulting vaccine strain stimulates a stronger immune response than a traditional live attenuated vaccine. Furthermore, Meissa is attenuating these non-essential virulence genes using a modern synthetic biology approach called codon deoptimization, known to be highly “tunable” and genetically stable.

Roderick Tang, CSO and cofounder of Meissa, explained, “Viruses, like RSV and SARS-CoV-2, are crafty opponents. They block our immune responses. The coronaviruses, including SARS-CoV-2, can easily mutate, which is what we are seeing happen with all the variants. To address this, we built our COVID-19 recombinant live attenuated vaccine on our optimized RSV vaccine platform, called AttenuBlock.”

Meissa’s goal is to create safe, potent, stable, and cost-effective intranasal vaccines, the backbone of which is its proprietary AttenuBlock platform, developed over ten years of research in Moore’s lab when he was an Associate Professor at Emory University.

By using synthetic biology—rational and precise codon deoptimization—hundreds of targeted mutations were made into the RSV genome to reduce the efficiency of translating viral mRNA into proteins by carefully selecting and replacing commonly used codons with nonpreferred codons in viral genes that inhibit the immune response, so the translation of these viral mRNAs into proteins becomes inefficient.

Thus, Meissa can deliver live attenuated vaccine candidates designed to increase antigen expression and decrease or eliminate the expression of genes that counteract the immune response, resulting in optimized genetic stability, immunogenicity, and virulence.

AttenuBlock is Meissa’s proprietary platform that uses synthetic biology to generate live attenuated vaccine candidates designed to increase antigen expression and decrease or eliminate the expression genes that counteract the immune response.

Meissa applies AttenuBlock to other targets by replacing the RSV surface proteins with those of the target of choice, in the case of SARS-CoV-2, with the spike protein, or with the human metapneumovirus (hMPV) surface protein or parainfluenza virus surface protein for its preclinical vaccine candidates.

Another thing that distinguishes Meissa’s vaccines is the intranasal method of delivery—directly in the nose. “If you can vaccinate at the site of a natural infection, this is something of a holy grail of vaccinology,” says Moore, “then you have the potential to not only prevent disease but also infection itself and really block transmission. For a respiratory virus, the natural point of infection is the nose.”

Vaccinating directly into the nose provides mucosal immunity. In phase 1 clinical trials, Meissa’s lead candidate, an intranasal RSV vaccine dubbed MV-012-968, was well-tolerated, appropriately attenuated, and stimulated a strong RSV-specific mucosal IgA response in adults and young children who had previously been infected and already had circulating antibodies to RSV in their blood.

RSV is a leading cause of infant respiratory infections such as bronchiolitis and viral pneumonia in infants. In the United States, approximately 1 percent of infants are hospitalized because of RSV each year. Globally, RSV causes more than 66,000 deaths per year and approximately three million hospitalizations in children under 5 years of age. Since the discovery of RSV in 1956, no vaccine has been approved for prevention.

The company also just started testing MV-012-968 in a phase 1c study in seronegative infants and young children. The study is enrolling up to 45 participants between the ages of six and 24 months at three sites in the United States to evaluate its the safety and immunogenicity.

“We believe that our intranasal live attenuated RSV vaccine candidate, developed on Meissa’s AttenuBlock vaccine platform, offers the potential to finally immunize against RSV, which has evaded other vaccine technologies for more than 60 years,” said Moore. “The development of a safe and effective RSV vaccine is a significant global health priority that could save thousands of lives and protect the health of millions of people around the world.”

Meissa’s second candidate is an intranasal recombinant live attenuated COVID-19 vaccine, MV-014-212, designed to protect against SARS-CoV-2 infection and transmission. Like Meissa’s RSV vaccine candidate, MV-014-212 offers significant potential advantages for global deployment, including needle-free intranasal administration, a single adjuvant-free dose to induce mucosal and systemic immunity, as well as a straightforward, economical, and scalable manufacturing process. A Phase 1 clinical study has been initiated in the U.S. to evaluate the safety, tolerability, and immunogenicity of a single intranasal dose of MV-014-212 ( identifier: NCT04798001).

While several vaccines are in use and many companies are developing vaccines against SARS-CoV-2, as long as it and its emerging variants continue to circulate, there will be a need for new vaccines, especially ones that are single dose, easy to manufacture, and easy to deliver. Meissa’s MV-014-212 vaccine targeting SARS-CoV-2 stimulates cross-neutralizing serum antibodies against the virus and variants of concern, and the company’s technology can generate new vaccine constructs to combat future variants.

Moore says its COVID-19 vaccine is well suited for global distribution—low cost, small footprint manufacturing, no needles, single dose, intranasal. “These are all important factors that Meissa’s COVID-19 vaccine can provide for worldwide accessibility, especially in developing countries,” he says. “In countries that already have injectable COVID-19 vaccines Meissa’s intranasal vaccine could also be an alternative to injected vaccines to help breach vaccine hesitancy and be an essential booster that adds a layer of mucosal immunity to protect against transmission.”


NEXT: More about the market opportunity and future goals

This is part of the Big4Bio Company to Watch program for July 2021: Meissa Vaccines.
For more information on the series, click here.