In the first of four features on Meissa Vaccines, Big4Bio spoke with Meissa Vaccines CEO Marty Moore about Meissa’s drive to deliver vaccines against respiratory infections, the technology behind their pipeline, its relevance in today’s post-pandemic world, and what the future holds for the company.
Company to Watch – Meissa Vaccines
Marie Daghlian
Meissa Vaccines is on a mission to solve a puzzle that has eluded scientists for decades—a pediatric vaccine against respiratory syncytial virus, or RSV.
Identified in the 1950s, RSV can cause serious respiratory tract disease in infants, children, and older adults. The World Health Organization estimates that RSV causes as many as 33 million serious respiratory infections a year resulting in more than 3 million hospitalizations and nearly 60,000 deaths in children under 5 years of age. Despite years of research by big and small pharmaceutical companies to develop a vaccine, no one has yet been able to develop one that is safe and effective in infants.
But Marty Moore, CEO and co-founder of Meissa Vaccines, plans to change that.
Moore has been working on RSV for more than 19 years, first as a professor in the pediatric infectious disease division of the medical school at Emory University. During that time, his lab developed a system for manipulating the genetics of RSV, which turned out to be a powerful technology for vaccine discovery.
In 2014, he teamed up with Roderick Tang, who had led RSV research and development teams at MedImmune for 11 years, to found Meissa Vaccines and bring the technology into the clinic.
At the time, no one told him that investors had little interest in vaccines and infectious diseases. Still the partners established a presence in Johnson and Johnson’s JLABS in South San Francisco, received seed capital in 2017 to work on their technology, and piqued the interest of Morningside, which provided the company with $30 million in series A funding in September 2019. Since then, Meissa has put together a strong team of vaccine specialists and moved two vaccine programs, one for RSV and one for SARS-CoV-2 (COVID-19) into the clinic, with a third program against metapneumovirus moving toward IND.
There are several ways to make vaccines, each of which is distinct, but all with the aim to confer immunity to an infection. Using a synthetic biology approach, Meissa has applied what it calls codon de-optimization specifically to the genes of the virus that block the immune response in the host to develop a proprietary technology focused on live-attenuated viral vaccines wherein the virus is weakened enough to be safe but still strong enough to provoke an immune response in the body.
“Doing so takes away the virus’s ability to block your immunity, ending up with a vaccine that is very attenuated yet gives you broad immunity like the natural pathogen,” says Moore. “Because live-attenuated viruses replicate like pathogens, they stimulate multiple arms of the immune system—innate responses like interferon and adaptive immune responses like B cells, which make antibodies that can prevent infection, and T cells, which clear virus.”
Other advantages of live-attenuated viral vaccines include single dosing without the need for a booster shot and generally more durable, long-lasting immunity. That’s because live-attenuated vaccines act like real pathogens. They also tend to be stable, easy to manufacture, and easy to distribute, making them ideal in places such as developing countries that lack the infrastructure for mRNA vaccines, for example.
The potential for live-attenuated virus vaccines to provide broader immunity, especially against variants—like the SARS-CoV-2 delta variant currently sweeping across Southeast Asia and many parts of the world that had quelled the initial strains—is another reason Moore is bullish on them.
“Here live-attenuated viral vaccines also typically do very well because unlike an injected mRNA protein where injected antigens are in a single protein shape or conformation, in a live virus vaccine, these proteins, like the spike protein on SARS-CoV-2 or the analogous fusion proteins on RSV, undergo dramatic conformational changes and in doing so they expose a broader range of epitopes that can be protective,” says Moore. “For example, in influenza, live-attenuated viral vaccines generally give broader protection against serotypes, and we saw broad coverage of our COVID-19 vaccine candidate in monkey studies.”
Back to addressing RSV, no one has yet succeeded in developing a pediatric vaccine. In the 1960s, the first injected vaccine tested, which was inactivated, resulted in severe disease in infants. When those children were vaccinated and then were later infected with naturally occurring RSV, they had severe respiratory disease that was not like natural RSV. That prevented testing of other non-replicating vaccine types in infants.
“Non-replicating RSV vaccines pose a risk of disease enhancement in RSV-naïve infants. These types of vaccines could be tested in the elderly, who have been previously exposed to RSV, but it was not clear whether they could be tested in infants. In contrast, live-attenuated RSV vaccines have been safely tested in infants, but safety attenuated candidates were poorly immunogenic,” says Moore. “It turns out that this is where our technology can really come into play, the crux of what we’re trying to do.”
Live-attenuated viral vaccine technology historically involves a balance between attenuation, which is related to safety, and potency, which is related to the immune response. If you weaken a virus until it’s safe enough to be given as a vaccine, the question is does it still give you a good immune response?
For RSV, what others found was that when you weaken RSV to the point where it is safe enough to give to a baby, it no longer provides a promising antibody response. There was no balance to be found to get both safety and potency. What Meissa has done that is innovative is to attenuate the virus using codon de-optimization specifically targeted to the immune modulating genes of RSV, in order to stop the virus’s ability to block host immunity and to end up with a vaccine that is safe yet provides robust immunity.
“Normally, for all other attenuated vaccines, you have to compromise the immune response, but what we’ve done is we’ve broken that balance. Our potency is no longer strictly dependent on the level of replication because of the unique way we have attenuated,” says Moore. “This technology is the backbone of Meissa.”
Meissa has already successfully tested its pediatric RSV vaccine in adults and older children in phase 1 trials and is currently testing it in infants, with a readout expected in the first half of 2022. Beyond that, the company’s phase 1 study of its vaccine candidate for COVID-19 will have a readout at the end of the second half of 2022.
Moore is hopeful. The pandemic struck a chord in everyone. Investor interest has turned in the company’s favor as it looks to raise a second round of capital with an eye to doing a crossover financing and an IPO.
“Vaccines have saved more lives in human history than everything except clean water,” says Moore. “I’m sad that it took a pandemic to increase interest but what’s clear is that these new platform technologies are what have value — adenovirus and mRNA have been around for a long time and they paid off. In infectious disease there is value in having a variety of platform technologies because one thing that we’ve learned from vaccine biotechs through those times of low interest is that plug and play doesn’t always work. The viruses are very diverse in their biology, they are very smart, and injected vaccines have their success and also their limitations. Live-attenuated viral vaccines are really a gold standard that, I think, we can develop to address other hard-to-tackle infections.”
NEXT: A deeper look at Meissa’s technology and pipeline programs
This is part of the Big4Bio Company to Watch program for July 2021: Meissa Vaccines.
For more information on the series, click here.