Thanks to CIDRAP Editorial Director Jim Wappes for alerting me to this very worrying report on his website by Stephanie Soucheray: Contrary dengue vaccine response hints at possible problems with Zika. Excerpt (but read the whole thing and follow the links):
"It's happened. We have a vaccine that enhances dengue," said Scott B. Halstead, MD, talking about a phenomenon whereby the dengue vaccine sets up dengue-naive recipients for severe disease.
Halstead, the leading figure in dengue research in the past 50 years, is referring to CYD-TDV (Dengvaxia, Sanofi Pasteur), the first dengue vaccine approved by the World Health Organization in April, and now licensed for use in five countries. When Halstead, a former senior advisor of the Dengue Vaccine Initiative and the founder of Children's Vaccine Initiative, first saw the 3-year results of the vaccine published in the New England Journal of Medicine last summer, he immediately saw a problem in the data.
“It's clear as the nose on my face: Vaccine recipients less than 5 years old had five to seven times more rates of hospitalizations for severe dengue virus than placebo controls."
ADE primes subjects for severe illness
Halstead is describing a problem dengue researchers feared for years; the vaccine appears to cause ADE, or antibody-dependent enhancement. In dengue ADE, which Halstead first identified, infection with one of the four strains of the virus produces antibodies to that strain and cross-reactive antibodies to the other dengue strains.
"Over time, you make and keep protective levels of antibody from the initial infection, but you lose the cross-reactive antibodies," said Halstead. "That allows a second dengue infection to cause severe illness, including dengue hemorrhagic fever."
Halstead said two examples illustrate dengue ADE in action: In 1977, Cubans, a dengue-naive population, were infected with dengue 1. Nearly 20 years later, in 1997, dengue 2 came to the city of Santiago, and hospital rates were eightfold higher in patients previously infected with dengue 1.
"The longer interval [between infection with different dengue strains], the more severe the disease," said Hallstead.
A similar phenomenon is seen in mothers who've had two or more dengue infections. They pass some cross-reactive antibodies to their babies, but no T cells, which are important in immune response. In turn, their children can react much worse to dengue virus.
What Halstead saw in Sanofi's data was the vaccine acting as an initial viral exposure in seronegative subjects (those with low antibody levels in the blood), almost like a mother and baby, leading to ADE in the years following immunization.
"The vaccine is even worse than an infection, because it has all different antibodies that wane over time, and the T cells from yellow fever," Halstead said.