Last year’s influenza vaccine also contained the same H3N2 strain as this year’s vaccine (A/Hong Kong/4801/2014 (H3N2)-like virus). Many people would have developed long term IgE mediated sensitization to the H3N2 viral proteins due to last year’s vaccine [1–4]⁠. Those who received the Flublok vaccine can be expected to have an even stronger IgE response due to its 3X viral protein content [5,4]⁠. This year’s vaccine H3N2 proteins would have been neutralized by these IgE antibodies. Thus resulting in the observed low vaccine efficacy. [6⁠]

When a person making anti-H3N2 IgE is infected with H3N2, one can expect the course of the flu to be significantly worse. So the “cytokine storm” being observed in severe cases is likely to be an infection concurrent with an allergic reaction. Death is caused by anaphylactic shock but due to the presence of an infection, it is wrongly classified as septic shock.

In the case of food allergy for example, the allergen exposure can be large enough to cause an immediate hypersensitivity reaction and anaphylactic shock within minutes/hours. In the case of influenza allergy, it may take a day or two for the virus to replicate and produce enough viral exposure for anaphylaxis. So the anaphylaxis unfolds over a couple of days.

“Self-reported vaccination for the current season was associated with a trend (P < 0.10) toward higher viral shedding in fine-aerosol samples; vaccination with both the current and previous year’s seasonal vaccines, however, was significantly associated with greater fine-aerosol shedding in unadjusted and adjusted models (P < 0.01). In adjusted models, we observed 6.3 (95% CI 1.9–21.5) times more aerosol shedding among cases with vaccination in the current and previous season compared with having no vaccination in those two seasons.” [7⁠]

This result makes a lot of sense. When you have influenza virus allergy and are infected, you have more mast cell degranulation, more histamine, more mucus, more sneezing, more viral shedding.

Increased hospitalization rates have been observed in asthma patients that have received the influenza vaccine. Again, this is as predicted because asthma patients are likely to produce stronger IgE responses to the viral proteins upon vaccination. [8⁠] On subsequent virus exposure, they can be expected to develop severe IgE mediated asthma.

Consider dengue infection. The initial mosquito bite that injects dengue virus into a person, causes the induction of IgE against dengue proteins. [9]⁠ Upon a subsequent bite that introduces the dengue virus again, the person develops hives due to a dengue specific-IgE mediated allergic reaction. As the infection (and thus allergic reaction) progresses and more histamine is released, vascular permeability increases. The result is hypotension and dengue shock syndrome. [10]⁠ Basically, a type 1 hypersensitivity reaction caused upon dengue virus exposure following IgE mediated sensitization to dengue viral proteins.

The route of exposure for natural influenza infection is the respiratory tract, not subcutaneous (SC) or intramuscular (IM) injection. Influenza vaccines artificially changed the route of initial viral protein exposure to SC or IM injection thus making it similar to the route of exposure for dengue. The result is an IgE response to influenza proteins, similar to the response for dengue. It should therefore not come as a surprise that we are modifying the course of influenza infection such that it is acquiring characteristics of a dengue infection (hives and shock).

As a result, allergy medications such as antihistamines and anaphylaxis treatments may have to be considered to avoid or treat this man-made influenza shock syndrome.

~ References ~

1. Smith-Norowitz T a, Wong D, Kusonruksa M, Norowitz KB, Joks R, Durkin HG, et al. Long term persistence of IgE anti-influenza virus antibodies in pediatric and adult serum post vaccination with influenza virus vaccine. Int J Med Sci. 2011;8(3):239–44.

2. Davidsson A, Eriksson JC, Rudblad S, Brokstad KA. Influenza specific serum IgE is present in non-allergic subjects. Scand J Immunol. 2005 Dec;62(6):560–1.

3. Nakayama T, Kumagai T, Nishimura N, Ozaki T, Okafuji T, Suzuki E, et al. Seasonal split influenza vaccine induced IgE sensitization against influenza vaccine. Vaccine. 2015;

4. Arumugham V. Short sighted influenza control policy based on poorly designed vaccines will sicken more people [Internet]. Available from: https://www.zenodo.org/record/1038445

5. Corporation PS. Flublok Quadrivalent 2017-2018 [Internet]. 2018. Available from: https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM524684.pdf

6. McLean HQ, Thompson MG, Sundaram ME, Meece JK, McClure DL, Friedrich TC, et al. Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons. Clin Infect Dis. 2014;59(10):1375–85.

7. Yan J, Grantham M, Pantelic J, de Mesquita PJ, Albert B, Liu F, et al. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Adamson W, Beato-Arribas B, Bischoff W, Booth W, Cauchemez S, Ehrman S, et al., editors. Proc Natl Acad Sci. National Academy of Sciences; 2018;

8. Joshi AY, Iyer VN, Hartz MF, Patel AM, Li JT. Effectiveness of trivalent inactivated influenza vaccine in influenza-related hospitalization in children: a case-control study. Allergy asthma Proc. United States; 2012;33(2):e23–7.

9. Koraka P, Murgue B, Deparis X, Setiati TE, Suharti C, Van Gorp ECM, et al. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity. J Med Virol. 2003;70(1):91–8.

10. Tuchinda M, Dhorranintra B, Tuchinda P. Histamine content in 24-hour urine in patients with dengue haemorrhagic fever. Southeast Asian J Trop Med Public Health. Thailand; 1977 Mar;8(1):80–3.

Written by Vinu Arumugham and published at BMJ ~ April 5, 2018.

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