The history of vaccine development and the effort to revolutionize vaccines to fight 21st century diseases

While the earliest documented examples of vaccination date to 10th century China, the first vaccine wasn’t developed until 1796; its target, smallpox, was eradicated worldwide in the late 1970s – a profound accomplishment.

There have been other notable successes using 20th century vaccine technology:

  • Diphtheria, mumps, pertussis, and tetanus: there has been a greater than 92% decline in cases and a 99% or greater decline in deaths due to these diseases using vaccines recommended before 19801.
  • Poliovirus, measles and rubella: endemic transmission has been eliminated in the U.S.
  • Smallpox was declared eradicated in 1979.

While there has been continued success and increased availability of vaccines over the last century, the development timelines have not shortened and many hard to treat diseases of the late 20th century continue to defy a vaccine solution despite billions of dollars being spent on their development. These diseases include:

  • HIV
  • Malaria
  • Tuberculosis
  • Herpes (HSV-1, 2; CMV)
  • Influenza
  • Cancer vaccines for a variety of malignancies

Much of the vaccine development effort has focused on using conventional vaccine technologies such as live attenuated (weakened or killed), inactivated, sub-unit, or recombinant antigens. More recently, the use of virus like particle (VLP) vaccines has gained attention with the successful approval of HPV (GARDASIL® and Cervarix®) and hepatitis B virus preventive vaccines. However, potential safety concerns associated with live/inactivated approaches as well as lack of broad immunogenicity associated with recombinant/VLP approaches has meant that new vaccine development has taken 30+ years from research to market. Indeed, for diseases like HIV and malaria there isn’t an effective vaccine on the market despite 30-50 years of determined research.

Today, a growing understanding of cancers and pathogens, the relatively new knowledge of genetics (genomics), and the advancement of other technologies has enabled the exploration of an array of new approaches to stimulate the immune system. Inovio is playing a leading role in the effort to develop a new generation of vaccine technology.

The timeline below shows key historical milestones in the development of vaccines and, most recently, one of the most important emerging vaccine technologies: synthetic vaccines. The newest developments may be instrumental in overcoming the weaknesses of vaccine technologies used to date, preventing and treating an array of diseases with unmet treatment needs and accessing significant commercial opportunities.

Vaccine and Inovio Milestones

17th c: Earliest documented examples of vaccination, from India and China
1724: Scientific description of smallpox inoculation submitted to the Royal Society
1796: Smallpox vaccine developed
19th c: Pasteur develops anthrax and rabies vaccines
1963: Measles vaccination introduced
1977: Last naturally-occurring case of smallpox
1991: Birth of DNA vaccines: four groups simultaneously present first data (Anderson, Chu, Robinson, Weiner)
1996: Inovio’s first data in small animals using electroporation and gene therapy
2005: First DNA vaccines approved for use in animals – infectious hematopoetic necrosis vaccine for salmon (Novartis Vaccines and Diagnostics); and first approved large animal DNA vaccine: West Nile virus for horses (Wyeth Animal Health – now Pfizer)
2007: WHO declares polio eradicated in the Americas, Europe, and Western Pacific
2007: First data from a DNA-based immunotherapy delivered using electroporation in humans
2008: Approval of first DNA-based product delivered using electroporation by any regulatory agency: growth hormone replacement hormone (GHRH) for use in swine by the Australian Pesticides and Veterinary Monitoring Agency (APVMA)
2008: First demonstration of SynCon® vaccines to induce cross-protective immune responses against deadly pandemic H5N1 influenza in ferrets and macaques
2008: NIH awards Inovio $23.5M to develop preventive HIV synthetic vaccine
2009: Inovio HIV synthetic vaccine delivered with electroporation shows superiority to HIV vaccine using Ad5 viral vector in primate study
2010: Inovio reports best-in-class T-cell immune responses in humans from cervical dysplasia therapeutic SynCon® vaccine delivered with electroporation
2011: Inovio reports best-in-class T-cell immune responses in humans from HIV preventive SynCon® vaccine delivered with electroporation
2011: Inovio reports that influenza SynCon® preventive vaccine delivered with electroporation induced functional antibodies in people and provided initial evidence of universal protection against multiple different strains with a single vaccine
2012: Inovio’s therapeutic vaccine for HPV-associated dysplasias and cancers demonstrates for the 1st time that a DNA vaccine can produce immune responses to kill target cells [Science Translational Medicine]
2013 Inovio’s DNA HIV vaccine achieves seven-fold increase (7% to 52%) in response rate of robust CD8 T-cells when delivered with electroporation [Journal of Infectious Diseases]
2013 Roche & Inovio enter into an exclusive worldwide license agreement to research, develop and commercialize Inovio's DNA immunotherapies targeting prostate cancer and hepatitis B
2014 Inovio’s VGX-3100 regresses late stage pre-cancer (CIN2/3) to CIN1 or no disease & clearance of associated HPV. This data provides the first validating evidence that DNA vaccine technology has the potential to fight cancers and infectious diseases.

1JAMA April 4, 2012, VOL 307, NO. 13, PP 1337-1447. Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States. Sandra W. Roush, MT, MPH; Trudy V. Murphy, MD; and the Vaccine-Preventable Disease Table Working Group