Vaccination for infectious diseases saves two to three million lives a year worldwide, according to the World Health Organization (WHO). Following the implementation of national programmes for immunization in the 1960s and beyond, many of the diseases that caused the majority of childhood deaths, such as diphtheria and polio, virtually disappeared. [1] The story of modern vaccines began with smallpox and Edward Jenner, but the history goes back even further.
The story of the smallpox vaccine
Humans have lived with infectious diseases for millions of years, with modern infections emerging around 11,000 years ago with the rise of agriculture. [2] Smallpox is likely to have appeared appeared in Africa around 10,000 years ago, and spread across Asia, Europe and the Americas. [3] During the 20th century alone, smallpox killed 300-500 million people worldwide.[4]
Attempts to vaccinate against smallpox seem to have begun in China and India as long ago as the mid-1500s or earlier. Known as variolation, the process involved deliberate infection with smallpox to trigger a mild form of the disease, to protect people against the deadly infection. While it reduced fatality rates, it unsurprisingly carried risks. [5]
After observations that people who developed cowpox were immune to smallpox, inoculation with material from cowpox lesions began in the mid-1700s. This was formalised by Edward Jenner in 1796 when he inoculated 8-year-old James Phipps with material from cowpox lesions from Sarah Nelms, a milkmaid. By the 1800s, the process of vaccination (from the Latin word vacca for cow) spread across Europe and the US.
While vaccines still play a vital role in infectious disease, the knowledge and techniques behind decades of research has allowed vaccination techniques to be applied in other areas of medicine.
Cancer vaccines: Therapeutic
Cancer immunotherapies, also known as cancer vaccines, are the most advanced vaccines outside of infectious disease. These teach the body's own immune system to recognise tumour-associated antigens on the tumour cell's surface and attack and destroy them. The main types of cancer vaccines are: [6]
● Made from the patient's own cancer cells or dendritic cells (autologous)
● Made from tumour-associated antigens found on the cells of certain types of cancer (allogeneic)
o Approaches include DNA, RNA/mRNA, protein/peptide and viral vector vaccines.
The concept of immunotherapy to kill cancer cells goes back to 1893, and the only cancer vaccine to be approved in the US (2010) and Europe (2014) so far was Dendreon Pharmaceuticals' sipuleucel-T (Provenge), indicated for the treatment of metastatic, asymptomatic or minimally symptomatic, metastatic castrate-resistant hormone-refractory prostate cancer (HRPC). The costs behind the production, and the issues around reimbursement, unfortunately led to the collapse of Dendreon and the slowdown in cancer vaccine research. [7-9]
Therapeutic cancer vaccines are in development for a wide range of indications, including: [9-11]
● Breast cancer
● Cervical cancer
● Chronic lymphocytic leukaemia
● Melanoma
● Non-small cell lung cancer
● Ovarian cancer
● Pancreatic ductal adenocarcinoma (PDAC)
Cancer treatments based on oncolytic viruses (viruses that attack cancer cells) can also be described as cancer vaccines. Amgen's talimogene laherparepvec, also known as T-VEC, or Imlygic, was the first oncolytic virus therapy to be approved worldwide, and is used to treat metastatic melanoma that cannot be surgically removed. [6, 12]
Cancer vaccines: prophylactic
While technically a vaccine against a virus, the herpes papillomavirus (HPV) vaccine plays a vital role in cancer prevention. HPV was first linked with cervical cancer in 1983, and the first HPV vaccine, Merck & Co's Gardasil, was launched in 2006. As well as reducing the risk of cervical cancer, HPV vaccines can also cut the incidence of vaginal, vulvar, penile, anal and certain mouth and throat cancers. [13, 14] A study in Scotland that...
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