Enhanced Disease in the Young in Year 3

Post #1306

There is currently a lot of hype about fast-tracking the approval of biologics such as mRNA products. There have been claims of going from zero to “in use” in 60 to 100 days. But history shows that we should not be approving new things that fast. An example would be the trial for Dengvaxia, a vaccine for Dengue Fever.

While short-term reports looked good, a report on the long-term effects included surprising harm found in those who were young and therefore more likely to have been “Dengue-naive” (never exposed to Dengue before receiving the vaccine). Here is the report:

The trial names below begin with CYD (chimeric yellow fever dengue) and end in a number. Here is a table showing that, in the CYD14 trial — and for those of age “2-5 yr” — the risk of hospitalization for Dengue among those vaccinated for Dengue was more than 7x the control group (second line of data):

[click to enlarge]

In the vaccine group, there were 15 out of 1,636 who got hospitalized for Dengue, while only 1 out of 813 in the control group was hospitalized for Dengue. Because these young kids had likely never been exposed to Dengue before receiving the vaccine, the vaccine had a chance to imprint their immune systems.

Future natural infection with another serotype of Dengue could then lead to enhanced disease, if their immune systems were only very specifically primed by vaccine. Even if all known serotypes of Dengue were combined into the same vaccine, it would be different than going through the natural infections of each serotype, in succession.

Another report combines the young kids from the CYD14 trial in the image above with the young kids from the CYD23 and the CYD57 trial:

Here is a twin-beta distribution that I created, showing the probability of various Dengue hospitalization rates for each group, given the observed data above:

[click to enlarge]

The blue curve represents baseline Dengue hospitalization rates compatible with the known data, the red curve represents those rates when young kids get vaccinated. The dotted vertical lines show that the upper bound of controls (blue) was still lower than the lower bound of the vaccine group (red). The baseline rate is about 0.2%.

But vaccinated kids had a hospitalization rate almost 5 times as large (~1.0%).

If you can find such clear evidence of danger 3 years after the original dose, then that means that the FDA should not be allowing new biologic products on the market inside of 100 days. They should not even allow new biologics on the market inside of 1,000 days (2.7 years). This harm from Dengue vaccine was found after 1,000 days.

Reference

[in one trial, vaccinated young kids had 7x the hospitalization risk of controls] — https://www.nejm.org/doi/full/10.1056/NEJMoa1506223

[in all trials, vaccinated young kids had 5x the hospitalization risk of controls] — Halstead SB, Russell PK. Protective and immunological behavior of chimeric yellow fever dengue vaccine. Vaccine. 2016 Mar 29;34(14):1643-7. doi: 10.1016/j.vaccine.2016.02.004. Epub 2016 Feb 10. PMID: 26873054. https://pubmed.ncbi.nlm.nih.gov/26873054/