For the first time ever, the World Health Organization (WHO) has recommended that pregnant women be vaccinated against respiratory syncytial virus (RSV), or that their newborns receive a dose of monoclonal antibodies to protect them against severe RSV disease, which has seen a global resurgence as the COVID-19 pandemic waned. 

In 2022-2023, RSV was the second most detected virus (10.9%) after SARS-CoV-2 (22%), after two seasons of low circulation, presumably due to pandemic-era restrictions. 

The new guidance on RSV, another new recommendation aimed at accelerating the pace of rubella vaccination in under-5s, as guidance on polio jabs and others, were all issued by WHO’s Strategic Advisory Group on Immunization (SAGE) at a press conference on Wednesday. 

The guidance came against data showing that routine vaccinations in 2023 still had not caught up with pre-pandemic levels. 

“In 2023, there were 14.5 million children who didn’t get even a single dose of vaccine.” noted  Dr Kate O’Brien, Director of WHO’s Department of Immunization, Vaccines and Biologicals, at the briefing.  

“Before we hit the pandemic, that number was 12.8 million children, so the world has not recovered back to the performance that was already achieved before we hit the pandemic.

World lags in vaccinating ‘zero dose’ children 

That leaves Gavi, The Vaccine Alliance, also behind on its target of reducing the number of ‘zero-dose’ children by 25% by 2025, the Alliance said yesterday in its annual progress report, also issued on Wednesday. 

However, there was good news for the Africa region, which was one of only two regions in the world that saw a decrease in the number of ‘zero dose’ children who have not been reached by any routine immunization programs. 

“The Africa region actually had a decrease in the number of zero dose children in 2023 compared with 2022 which is really good news,” O’Brien said. 

“And in addition to that, the Africa region was one of, again, a limited number of regions that also had a decrease in the number of children who did not receive a measles vaccine. That has fallen to 11.5 million children, compared with 12.2 million children in 2022,” O’Brien said. 

Progress globally in HPV vaccination 

Both SAGE and Gavi report also noted progress on the drive to eliminate cervical cancer by immunizing 14 million girls with the HPV vaccine. There too, the African region stood out with the greatest gains in immunization rates of almost any other region in the world, O’Brien said.  

“With 14 million girls vaccinated against HPV with Gavi support… this number is greater than the previous 10 years combined.” said Gavi in a press statement. “Gavi has now helped prevent over 600,000 future deaths from cervical cancer alone and is on track to reach 86 million girls by the end of 2025.”

RSV recommendation includes two options  

The RSV recommendation to countries comes in two parts: either introduce the new RSV for pregnant women in their third trimester to protect their fetus against congenital RSV, preventing the disease in newborns. Alternatively, countries might opt to administer a single dose of monoclonal antibodies to the newborn babies themselves, the SAGE panel recommended.

There are pros and minuses of each approach. The RSV monoclonal antibody remains very expensive to procure. But clinical vaccine trials also have indicated a safety “signal” of slightly more pre-term births among women who get the vaccine – although the increase was very small and  outweighed by the survival gains of newborns whose mothers were vaccinated.

“Close to 97% of the [RSV] related mortality is estimated to occur in low and middle income countries,” said SAGE chair Dr Hanna Nohynek. “We now have, after 60 years of waiting, … two interventions to prevent RSV in children, that is maternal immunization and then monoclonal antibodies to small children.

“SAGE recommended that all countries should introduce passive immunization to prevent severe RSV disease in children, and that could take place either by maternal vaccination or by this monoclonal antibody.  

“In the vaccine efficacy studies, there was a documented safety observation of imbalanced preterm delivery in two trial sites with maternal vaccination, mainly in South Africa and Argentina, and SAGE looked into this signal. But considering the risks and the benefits, and clearly there is a major benefit to be expected,” she said, adding that researchers would continue to collect more data on the pre-term birth issue. 

Rubella vaccine recommended universally

In another piece of significant, but technically nuanced advice, SAGE also recommended that rubella vaccine be administered “universally” in countries, even if they haven’t yet reached an  80% rate of measles vaccination. 

About 32,000 infants a year are born with congenital rubella syndrome, an insidious form of the disease that causes severe heart defects and intellectual disability. Those cases mostly occur in just 19 countries with historically low overall vaccination rates. 

Previous WHO recommendations held that countries should achieve 80% coverage with at least an initial dose of measles vaccine – with measles being used as a proxy for a country’s immunization outreach capacity.  

That was due to concerns that in countries with low-vaccination rates overall, introduction of the rubella vaccine could actually increase environmental exposures of girls and pregnant women to the rubella virus overall, and thus cause even more CRS cases in newborns. 

But new modeling work and analysis shows that the 80% threshold rate is “overly conservative and no longer warranted,” the SAGE experts said in a press statement.  

Six of the 19 remaining countries with no rubella containing vaccine (RCV) are now planning to introduce it, and SAGE recommends that the vaccine thus be introduce in the 13 remaining countries.

“The universal introduction of RCV, accompanied by wide age-range campaigns at introduction, should be initiated in the remaining 13 countries. Regular follow-up campaigns are recommended in countries where routine MCV coverage is below 90%,” SAGE said.

Reinforcement of polio vaccines 

SAGE also recommended that during polio outbreaks, and subsequent vaccine campaigns, a jab of inactivated poliovirus (IPV) be administered along with the oral polio vaccine (OPV), so as to better reinforce the immunity of children at risk.

Adding the injection would help better protect against environmental exposures to vaccine-derived poliovirus, in outbreaks such as the one seen recently in Gaza, as well from exposures to wild poliovirus, still circulating in countries such as Afghanistan and Pakistan, WHO said, adding “unless it would impact the timeliness of the response.” 

Currently, WHO and country partners are in the process of phasing out the bivalent OPV and replacing it with a novel OPV vaccine that does not mutate as easily in the environment to cause new infections in other young children. 

However, two doses of OPV are needed to build the required immunity, with a weaker response in undernourished children, while recent studies have shown that the IPV has a reinforcing response in the gut to the OPV vaccine, whatever type was administered, as well as protecting from polio’s most severe outcome, paralysis, and that is a boost to at-risk children generally.  

“The whole intention here is to shift over to a world where we no longer give oral polio vaccine, but we are relying in that end stage of polio eradication on injectable form of of the vaccine,” pointed out O’Brien, noting that in most developed countries that shift has already happened, and IPV is the only vaccine that infants and young children already receive.

“So including the injectable polio vaccine along with the oral polio vaccines whenever there’s an outbreak,… and including the injectable form of the polio vaccine for the preventive campaigns, wherever that is possible, provides a sort of dual protection in order to enhance the immunity and to protect against the possibility of circulating [vaccine-derived] strains that could transform into ones that that cause paralysis.”

Weighing vaccine costs, benefits and scientific evidence 

Cutting across all of the WHO’s recommendations are issues of vaccine costs, as well as nuanced considerations of benefits that can be obtained – and the gaps in knowledge that countries must weigh up in decision-making. 

“Fifty years ago, there were seven diseases against which we have vaccines today. Today there are over 30 diseases that are vaccine preventable. And there has been a huge success rate in developing vaccines in the past 15 to 20 years,” O’Brien said, leading to “more vaccines available than any country can take up.”

More and more vaccines are constantly being developed, particularly with the recent introduction of new technologies, such as mRNA. That leaves countries forced to weigh up an increasing array of factors, including the scientific evidence and data around relative costs and benefits of various choices. 

“So we’re really in a new era of vaccine development and vaccine deployment,” she said. “But it really depends also on the characteristics of the disease and the characteristics of the vaccine relative to that disease, in order to achieve that ultimate end point of disease prevention, which is the most equitable kind of disease prevention we could ever have, which is complete eradication of the disease

But the increase in vaccine options also means that more and more countries are struggling with questions around the evidence of a vaccine’s benefits against costs, and many of the newest vaccines and solutions may also remain out of reach until prices come down.

Price drops usually only happen when a vaccine becomes available in generic form or agencies such as Gavi procure the jabs in bulk on behalf of low- and middle-income countries.  

“Vaccine is not a prevention tool unless it’s actually used,” O’Brien remarked.  “And so this is at the heart of vaccination programs: that they get to the countries that need them.”

Image Credits: Flickr – UNICEF Ethiopia, University of Oxford/Tom Wilkinson, UNICEF, NIAID, WHO, WHO.