TRANSLATIONAL RESEARCH SCIENCE exists to insure that an ethical and logical process is followed that leads to warranted scientific claims from clinical research. This means phased research studies that meet regulatory requirements.

In drug trials, pharmacologically active components of drugs - as well as inactive components must be dosage safety tested in animals to ensure that Phase I clinical trials place human subjects at minimal or reasonable risk. Studies include dose variance studies, and then if all seems well, Phase II small safety trials can proceed.

In the study of biologics, a different category of pharmaceutical products, only the protein components are required to be dosage-safety tested in animals. Health outcomes of vaccines, for example, are routinely testing in animals prior to use in humans. Take, for example, the vaccine safety studies conducted on animals for the SARS and MERS viruses.

In SARS, a type of “pathogenic priming” of the immune system was observed during animal studies of SARS spike protein-based vaccines. The exposure of vaccinated animals to the SARS virus led to increased morbidity and mortality. The problem, highlighted in two studies, only became obvious following post-vaccination challenge with the SARS virus. A study in 2006 by Deming et al. reported that recombinant SARS spike-protein-based vaccines failed to provide protection from SARS-CoV infection - and also that the mice experience increased immunopathology with eosinophilic infiltrates in their lungs. Previously, Weingartl et al. (2004) had found that ferrets previously vaccinated against SARS-CoV developed an dangerously strong inflammatory response in liver tissue (hepatitis). Both studies suspected a “cellular immune response".

These types of unfortunate outcomes are sometimes referred to as “immune enhancement”; however, this term seems euphemistic and it fails to convey the increased risks of morbidity and mortality due to prior exposure to the SARS spike protein. I prefer to use the term “pathogen priming”; specifically pointing to the peptides in the vaccine (or the virus) with pathogenic potential as “putative pathogenic priming peptides”.

Pathogenesis from vaccines is not new, nor should they be considered unexpected. They truly are only unanticipated when those who develop them do not include available background knowledge in their translational research plan. An example is the H1N1 influenza vaccine used in Europe that led to narcolepsy in some patients. The narcolepsy resulted from homology between the human hypocretin (aka, orexin) receptor 2 molecule and proteins present in the vaccine. The causal link was established following the detection of cross-reactive antibodies in the serum of patients who developed narcolepsy after H1N1 vaccination in Europe (Ahmed et al., 2015).

Just as in the SARS-CoV animal studies, Agrawal et al., (2016) reported that mice vaccinated against MERS-CoV (Middle East Respiratory Syndrome) development exaggerated pulmonary immunopathology when challenged with the MERS virus following vaccination. They observed lung mononuclear infiltrates in all groups after virus challenge, and they reported that increased infiltrates that contained eosinophils and the eosinophil promoting IL-5 and IL-13 cytokines were seen only in the vaccinated animals.