Except for AstraZeneca’s infant-approved respiratory syncytial virus (RSV) vaccine in the U.K., there is a wealth of RSV vaccines expected to come out of the pipeline this year, for varying target populations, said a public health expert.

The session on emerging vaccines on day three of the Global Vaccine and Immunization Research Forum (GVIRF) conference in Incheon introduced the progress with dengue virus vaccines, respiratory syncytial virus (RSV), the Group B Streptococcus (GBS) vaccine, shigella, and enterotoxigenic E. coli (ETEC).

However, the main focus this year seems to be on the race toward RSV vaccines, said Professor Ruth Karron of Johns Hopkins University, School of Public Health.

“RSV vaccines have been totally revolutionized by the work of Barney Graham and Jason McLellan who solved the structure of the RSV by figuring out a way to stabilize the RSVF protein in the prefusion conformation,” she said.

She especially credited those who participated in clinical studies during the pandemic saying, “Not only is it hard to do studies in a pandemic setting, but RSV seasonality completely changed and RSV was elusive for a couple of years and then showed up at unexpected times.”

According to recent estimates, RSV is the leading cause of global pneumonia in young children. Statistics show that there are 33 million cases of lower respiratory tract infection, 3.6 million hospital admissions over 100,000 deaths each year, and more than 95 percent of these deaths occur in low and middle-income countries (LMICs). It also causes lower respiratory tract illness in older adults, she added.

At the same time, she explained, “We have good data in high-income countries but considerably less robust data from LMICs, which can deter RSV vaccines from reaching these populations where the disease burden is highest due to lack of data.”

She mentioned two passive immunization strategies for infants.

There is the maternal immunization route with the RSV fusion protein or the administration of a long-acting vaccine like a monoclonal antibody with a prolonged half-life, that can protect the infant for the first several months of life, according to Karron.

Meanwhile, there are live attenuated vaccines in development for older children of age 6 months and older and then RSV subunit and vectored vaccines for older adults.

She particularly highlighted three RSV vaccines that showed substantial efficacy in older adults from Janssen, GSK, and Pfizer. However, she said despite showing good vaccine efficacy, Janssen recently announced that they will no longer be pursuing its RSV vaccine candidate which she attributed to the fact that other candidates were more advanced in development.

Consequently, GSK and Pfizer are now leading the charge with RSV vaccines in adults in regulatory review.

Regarding the maternal RSVpreF vaccine developed by Pfizer, she noted that the trial was conducted in 18 countries but unfortunately, there were only two LMICs that participated in this trial.

Accordingly, FDA approval is expected this year around Q3 and there are many other submissions in process, she said.

The other infant vaccine which has already been approved in the U.K. last year with an FDA review also expected this year is the monoclonal antibody, nirsevimab. It is being developed jointly by AstraZeneca and Sanofi as a single dose given to babies under six months of age to protect them through the RSV season. Additionally, it showed substantial efficacy against all endpoints and also demonstrated protection against all-cause lower respiratory tract infection (LRTI) and all-cause LRTI with hospitalization.

She further applauded AstraZeneca’s study as it also showed that the number needed to prevent one all-cause medically attended lower respiratory tract hospitalization is 53 and 57 days of hospitalization averted for every 1,000 infants, providing policymakers with useful insights.

She also drew attention to another RSV vaccine for infants being developed by Merck which is currently in phase 3 clinical trials despite showing limited efficacy in previous studies. She also noted two other early phase studies which are still ongoing from Meissa and Sanofi.

However, Karron maintained, “Even with all this buzz around the RSV vaccines this year, there is still substantial work to ensure implementation and uptake to protect infants in LMICs which has the most vulnerable population.”

In this regard, the public health expert noted that the Bill and Melinda Gates Foundation (BMGF) will help fund the development of an affordable multidose vial for the delivery of the vaccine in lower-income countries. This is important to drive greater vaccination coverage as studies suggest that multi-dose vaccine vials translate into greater economic-logistic advantages due to lower packaging and storage costs with significant environmental benefits accrued from reduced medical waste generation.