Yellow Fever Vaccine Potency Wanes Over Time

SEATTLE — A single-dose of vaccine for yellow fever (YF-VAX strain 17D-204) is touted as offering lifelong protection, but the jab’s potency was reduced over time, researchers reported.

In blood samples from 22 flavivirus-naïve individuals that were vaccinated for yellow fever within the last 10 years, 9% were 17D seronegative, and almost all (n=21/22) were seronegative for more than 95% of the South America 1 wild-type strains, according to Felicity J. Coulter, a PhD candidate at Oregon Health and Science University (OHSU) in Portland.

In a MedPage Today interview at the American Society for Tropical Medicine and Hygiene (ASTMH) annual meeting, Coulter said that the finding “really raises an important question, in terms of the design of the 17D vaccine and what type of boosting regime we do, whether or not it’s still appropriate?”

The researchers tested participants for seropositivity levels NT50 and NT90 (the reciprocal serum dilution resulting in a 50% or 90% reduction in infectivity) against six virus strains in all 22 individuals.

Significantly reduced potency of neutralizing antibodies was seen in certain strains. “A high proportion of individuals were seronegative for wild-type and south America 1 strains in particular,” Coulter told Medpage Today. The yellow fever strains were:

• 17D strain (the parent)
• BA-55 (Nigeria 1986)
• BC-7914 (Kenya 1983)
• 614819 (Panama 1974)
• BeH622205 (Brazil 2000)
• Br/MG/2001 (Brazil 2001)

All participants (ages 20-70 years; 59% female) had some level of protection to 17D, but for the Nigerian strain, 86% (n=18/22) were NT50 seropositive, which reduced to 41% (9/22) when challenged at NT90. Similarly, the Brazilian 2001 strain produced antibodies in 95% of participants (21/22) at N50 but only 41% (9/22) at NT90, they reported in an ASTMH poster.

The most striking finding was that no participants had seropositivity for the Panama strain, and only one person (4.5%) had good neutralizing antibody response to the Brazilian 2001 strain. “But interestingly, that person didn’t have good titers to any other South American 1 strain. I suspect this individual probably traveled to South America in the last 10 years, and experienced some kind of subclinical infection and therefore had a boost,” Coulter said, but stressed that this was just a theory.

A separate ASTMH poster looked at antibody response to yellow fever vaccine neutralizing antibodies beyond 10 years. Bettie Kareko, also a PhD candidate at OHSU, reported that in 18 individuals who were vaccinated more than a decade ago (range 10.29-60.62 years), there were varied immune responses. She explained one participant “had no detectable neutralizing antibodies,” while another who had been infected with the Zika virus also had no detectable antibodies to yellow fever, and “one participant who had the vaccine 50 years before, mounted a high immune response.”

“Some people fall off below the limit of detection,” she stated.

Kareko and colleagues did not gather data on the participants’ previous yellow fever infection history, noting that “A lot of yellow fever is asymptomatic, so that’s a good question.”

Still, “people traveling to South American regions maybe be at high risk of not being protected,” she cautioned. “In the future, we should think about redesigning the vaccine.”

Maggie Suzanne Jennave McCarter, a PhD candidate at the University of South Carolina in Columbia, told MedPage Today that the data were interesting, but that she’d like to see “a subgroup analysis on titer response given various demographic information, such as BMI category and age.”

Jennave McCarter, who was not involved in the studies, pointed out that there are “conflicting opinions on whether or not a 10-year booster is needed for yellow fever; in particular, older populations may need the booster more than younger populations.”

Yellow fever is endemic in 34 countries in Africa and 13 countries in South America, and is passed to humans by an arbovirus through infected Aedes and Haemagogus mosquitoes.

When the yellow fever vaccine was originally licensed in 1938, a booster shot was recommended every 10 years. In 2016, the World Health Organization (WHO) recommended a single lifetime dose. Coulter argued that may be inadequate especially for people who travel to endemic countries.

“The data informing that [WHO] decision was largely from endemic countries, showing that a large portion of individuals had long-lasting neutralizing antibodies beyond 10 years,” Coulter explained. “But new dosing regimen from WHO “was to mitigate a shortage of the vaccine at that time,” such as during a yellow fever breakout in Brazil in 2017-2018 that was thought to be caused by the forest-dwelling Haemagogus, not Aedes Aegypti, an urban mosquito.

When vaccines became available in affluent neighborhoods in Brazil, Newsweek reported that gang boss Thomaz Viera Gomez kidnapped nurses to force more equitable distribution of the vaccine to low-income neighborhoods.

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