by Stephene Rose
Senior Study Director, Drug Safety
The science of immunogenicity began similarly to how today’s medical breakthroughs occur: with a carefully reasoned hypothesis.
In 1796, English physician Edward Jenner noticed that milkmaids who contracted cowpox, a relatively non-threatening skin disease, were usually immune to the much deadlier smallpox disease. Thinking that inoculation with pus from cowpox blisters might protect a person from smallpox, he tested his hypothesis on the eight-year-old son of his gardener.
Fortunately, Jenner’s idea worked – and the practice of vaccination went on to save millions of lives over the next two centuries.
Of course, modern medical research sets much higher standards than in Jenner’s day. Ethical tenets, scientific practices, and strict regulatory rules demand far more rigorous testing before a vaccine, or any drug, is tested in humans. Meeting those standards requires effectively designed preclinical studies, led by knowledgeable and experienced science partners, to assess the safety and promise of vaccine candidates.
In my last blog, I explained the continuing need for breakthrough vaccines. Here I’ll cover the elements of a quality preclinical package for evaluating them:
Bioinformatics, which involves analyzing biological data to predict toxicity. Experts in this field tap rich databases and use sophisticated information systems to drive decisions on potential vaccines early in development.
In vitro analysis, using an array of scientific techniques and technologies to evaluate the pharmacologic activity of a vaccine. These tests can signal whether a compound is safe and potent enough for further testing.
In vivo analysis, testing a vaccine’s safety and effectiveness in a selected animal model before first-in-human clinical trials. These tests cover important areas:
- Efficacy and safety – selecting the safest and most effective dose;
- Single-dose acute toxicity tests – measuring toxicity after one inoculation (not always required depending on the species used and the type of vaccine under study);
- Repeat-dose toxicity tests – assessing toxicity of a compound administered repeatedly over a set period of time (meets Good Laboratory Practices and covers key parameters, e.g., ophthalmology examinations, FDA-approved Draize Test score of the injection site, body temperature, electrocardiograms, body weight, food consumption, histopathology, and a range of clinical pathology measures);
- Biodistribution – how long a compound stays in the body and how it is eliminated;
- Immunopharmacology – evaluating the potential of a vaccine to protect against a disease and demonstrating the reversibility of any immunopharmacologic effects (may involve assessing acute phase proteins, histopathology and specific clinical pathology measures, and may be combined with a repeat-dose toxicity test for a detailed evaluation of the compound); and,
- Local tolerance – evaluating the injection site using Draize scoring and histopathology, usually in combination with a repeat-dose toxicity test.
If a vaccine candidate targets women of child-bearing age or children, reproductive toxicology studies may be needed. Separate safety pharmacology studies come into play if a test vaccine has any possibility of impacting the cardiovascular, respiratory, and/or nervous system; parameters such as body temperature and electrocardiograms would be measured in a repeat-dose toxicity study to evaluate these potential effects.
Having a robust, high-quality preclinical study package is just one element, albeit critical, for evaluating the next breakthrough vaccine. Success in medicine’s ongoing war on infectious diseases relies heavily on partnership—between the CRO and the Sponsor – and between the broader communities involved in vaccine research, from research scientists to biopharmaceutical companies and to government regulators.
The stronger this partnership is, the more effective we will be in turning a carefully reasoned hypothesis into a life-saving vaccine.
Stephene Rose, BS, MBM, is Senior Study Director of Drug Safety at MPI Research. To find out more about our preclinical development capabilities for vaccine candidates, contact firstname.lastname@example.org.