Answering the WHO Call for a GBS Vaccine

Streptococcus agalactiae, also known as Group B streptococcus (GBS), is a leading cause of neonatal and infant sepsis and meningitis, as well as a cause of stillbirth and preterm births. Neonates and infants up to three months bear the highest burden of GBS disease, with premature infants with early-onset GBS carrying the highest mortality rate (20 percent) (1). The highest burden is in the low-income countries of Africa, where more than half (54 percent) of estimated invasive GBS cases and almost two thirds (65 percent) of all fetal/infant deaths occur (2).

The challenge is not exclusive to African nations, however. A 2017 study suggests that around 18 percent of pregnant women carry GBS worldwide (3). Antibiotics can reduce the incidence of early-onset GBS disease, but do not prevent GBS disease beyond the first few days of life. Since GBS occurs in neonates and infants with as yet ineffective immune systems, the WHO targeted pregnant women by putting out a call for an effective maternal GBS vaccine that could protect infants through transplacental transfer of maternal antibodies. Danish biotech MinervaX answered the call and is in the process of developing a novel, prophylactic vaccine against GBS, for which CDMO Wacker Biotech will manufacture the active protein ingredients. We speak with Bjørn Kantsø, CTO and head of CMC at MinervaX to learn more.

What factors prompted the demand for a prophylactic vaccine targeting Group B streptococcus?
 

There are no licensed vaccines against GBS – only prophylactic antibiotics. With these, there's a very short window for treatment and a pregnant person can still transmit GBS. It doesn't necessarily affect the mothers, per se, but it can, if transmitted to the unborn fetus or newborn baby, have a severe impact, including death, preterm birth, or a life with comorbidities.

The WHO estimated a need for at least 120 million doses of this vaccine to be produced each year.

What are the challenges in developing the vaccine and reaching the right number of doses?
 

Developing and licensing a commercial vaccine is always tricky, but the real challenge with GBS lies in the low incidence rate. A low incidence rate means that an efficacy study will be very large, and likely too large to feasibly execute. As an alternative, MinervaX is working to develop a surrogate endpoint marker of efficacy, which we are in discussions with the regulatory authorities about. Manufacturing scale may also be challenging if up to 120 million doses are to be supplied annually according to the expected global demand.

The task of manufacturing requires somebody that can produce at large scale. Luckily, it’s a vaccine. In a vaccine, the active ingredient content is quite low, so from a manufacturing point of view, it's not such a big task, but it does require collaboration with CDMOs that can deliver. We signed an agreement with Wacker Biotech. They will produce the active ingredients for our vaccines.

What about challenges regarding accessibility?
 

The vaccine is needed in high, middle, and low-income countries. It's always difficult to go to low-income countries; to foster a distribution network and get access for patients. We're lucky because vaccines may be distributed via public health organizations like GAVI to low-income countries, and the vaccine will be going to pregnant people. The majority of pregnant people are seen regularly by midwives and doctors, which means it’s easier to get drugs and vaccines to them. 

Much has happened in the world of vaccines in recent years. Do you think the world generally has become more critical or more appreciative of them?
 

I think the world has become much more appreciative of vaccines. There are, of course, some people who make a lot of noise, but they’re few. In general, the COVID vaccines saved many lives.

What would you say to those people?
 

Well, we must accept that the decision to take or not to take a vaccine is an individual choice. All we can do is make sure we provide objective information about the benefits and combat misinformation, of which there tends to be a lot among anti-vaxxers. I once heard a very clever man say that when a vaccine works well, the only thing you see are the side effects. Unfortunately, there are usually at least some mild side effects with vaccines (usually a sign of them working to boost the immune system) and – luckily – serious side effects are very rare. Generally, the benefits vastly outnumber the risks, and there is no medicine in the history of mankind that has saved more lives than vaccines. Luckily, our vaccine seems to have a very favorable safety profile with mostly mild to moderate injection site reactions, and we have not seen and don't expect any serious side effects. After all, we are only injecting small bacterial components that we have all been exposed to during a lifetime of exposure to GBS, and to which most of us already have some degree of pre-existing immunity.

How satisfying would it be to be successful in this project?
 

We can't go into low-income countries without the approval of the WHO or GAVI. It's impossible to make vaccines accessible to those who need them without collaborations of this kind. If we're successful then millions of babies’ lives will be saved. That's a major thing for me personally, but also for the company and for the world. If you aren’t driven by that, I don't know what will drive you.

My hopes are that we can launch a full program and get it out to the people who need it. We have our CDMO in place and I feel that they will be a robust partner.  We have secured our manufacturing network now and we are well on our way to providing a GBS vaccine to the world.