Dr. Tetyana's Perspective
on Vaccination and Natural Immunity
By Tetyana Obukhanych, Ph.D.
In 2012, Tseng et al. published a seminal paper in PLoS One describing the effects of several SARS-CoV vaccine candidates on subsequent challenge of research animals with SARS virus. Vaccinated mice developed anti-SARS antibodies and were protected from viral infection upon challenge. However, their lung showed a serious type of immunopathology in response to post-vaccinal virus exposure – pulmonary eosinophilic infiltration. The authors cautioned against application of these vaccines in humans.
What are eosinophils and why their infiltration of the lung is dangerous?
Eosinophils are white blood cells that are part of the immune system mediating allergic and hypersensitivity reactions. Their infiltration of tissues can lead to serious disease.
A world leading hospital in respiratory care, National Jewish Health, gives a succinct description of eosinophilic lung disease:
“Eosinophilic pneumonia describes a category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory condition of the lungs, involving the air sacs. When the lungs are inflamed, they become swollen. This can result in low oxygen in the bloodstream.”
“Symptoms [of acute eosinophilic pneumonia] include wheezing, chest tightness, cough, chest pain, increased phlegm (mucus), shortness of breath and rapid breathing. It may involve bloody mucus, fever, muscle aches, decreased oxygenation, and even respiratory failure. Acute eosinophilic pneumonia results from excessive activation of type-2 immune cells and production of type-2 cytokines such as interleukin-5. This results in excessive influx of eosinophils in the lung.”
While keeping in mind the work of Tseng et al. on SARS-CoV vaccines, let’s look at a recent publication in Science by Gao et al. on the SARS-CoV-2 vaccine candidate called PiCoVacc.
Gao et al., while citing prior findings about SARS-CoV vaccines including those of Tseng et al., have performed their analyses of PiCoVacc safety and found no immunopathology in their research animals. This outcome is surprising, given that PiCoVacc was prepared in the same fashion as one of the four vaccines studied by Tseng et al.
In short, PiCoVacc is SARS-CoV-2 virus grown in Vero cells, inactivated with beta-propiolactone and mixed with alum-adjuvant. Similarly, the ‘BPV’ SARS vaccine (from Tseng et al.) was SARS-CoV virus grown in Vero cells, inactivated with beta-propiolactone and mixed with alum-adjuvant. Given that SARS-CoV and SARS-CoV-2 are related viruses and their corresponding vaccine preparation process was the same, why did Gao et al. fail to observe lung immunopathology upon viral challenge of vaccinated animals, whereas Tseng et al. did?
The answer may lie in the details of how the experiments were performed. While Tseng et al. performed lung tissue analyses of their vaccinated animals on day 2 post-viral challenge, Gao et al. waited 7 days after challenge. Furthermore, Tseng et al. used a procedure specific to the detection of eosinophils (by using eosinophil-specific MBP protein stain of lung tissue sections), whereas Gao et al. relied upon simple H&E (hematoxylin & eosin) histology stain that can only show overall cell morphology.
Gao et al. concluded that their PiCoVacc data “support clinical development of SARS-CoV-2 vaccines for humans,” even though they may have simply missed detecting a vaccine-induced predisposition to immunopathology by performing superficial histologic analyses on a wrong day post challenge.
Furthermore, their additional inquiry into any other indications of immunopathology, such as hematological, biochemical, and cytokine profiles, was carried out only following vaccine administration (which was never the issue raised with SARS-CoV vaccines) rather than after post-vaccinal viral challenge.
Following Gao’s day 7 (instead of Tseng’s day 2) post-exposure time point, another research group studying animals vaccinated with the ChAdOX1 (Oxford) CoV-19 vaccine and then exposed to the virus, also conveniently concluded that they didn’t find any such immunopathology.
Needless to say, these publications cannot assure us about public health safety of CoV-19 vaccines under development, until such time that they are tested in research animals using proper time points and more detailed immunohistologic analyses, such as the ones originally performed by Tseng et al.
Tetyana Obukhanych, Ph.D. is Immune Science Educator at BBCH (Building Bridges in Children's Health), an online community of parents and doctors dedicated to learning the science that impacts children's health and committed to the principle of informed medical consent.