How Therapeutic Vaccines Work

Not all vaccines are used to prevent infection. Traditionally, vaccines stimulate the immune system so that it can block disease-causing organisms (pathogens) from establishing an infection. There are other newer forms, called therapeutic vaccines, that stimulate the immune system so that it can treat certain diseases and/or slow their progression.

Although the field of therapeutic vaccines remains largely experimental, there have been three vaccines created so far that have been approved for use by the U.S. Food and Drug Administration (FDA).

Person receiving a shot
Jeffrey Hamilton / Digital Vision / Getty Images

Much of the focus of current research has been placed on creating therapeutic vaccines for cancer, but other scientists are aiming to develop therapeutic vaccines to treat HIV, human papillomavirus (HPV), viral hepatitis, cholera, and other potentially serious diseases.

How They Work

In the same way that traditional vaccines stimulate the production of antibodies to target specific pathogens (like viruses or bacteria), therapeutic vaccines stimulate the immune system to target cancer cells or control progression chronic infections like HIV.

Unlike traditional vaccines that are given before a person gets a disease to defend against infection, therapeutic vaccines are given after a person gets a disease to mount a more robust, disease-specific offense.

There are two different approaches to the development of therapeutic vaccines:

  • Autologous vaccines are a form of personalized medicine in which cells from a person's own body (such as cancer cells or immune cells) are harvested to make a vaccine for that person.
  • Allogeneic vaccines are created from cells that are harvested from others and/or engineered in the lab. It is the approach most commonly used to develop therapeutic vaccines for cancer.

From these cells, scientists can create different types of therapeutic vaccines with distinct mechanisms of action. These include antigen vaccines, dendritic vaccines, and DNA vaccines.

Antigenic Vaccines

Antigenic vaccines involve substances the provoke a specific antibody response, knows as antigens. The antigen may be a live attenuated (weakened) pathogen, an inactivated (dead) pathogen, a subunit (fragment) of a pathogen, or a substance produced by a pathogen.

These include tumor antigens produced by cancer cells that, when harvested and introduced into the body, amplifies the immune response to better fight the cancer cells from which they were produced.

Dendritic Vaccines

Dendritic vaccines involve a type of white blood cell called a dendritic cell that is part of the body's innate immune system. These are the frontline cells that sentinel for pathogens and attack before the immune system is able to launch a disease-specific antibody response.

By harvesting these cells and inoculating them with cancer cells or inactivated viruses, it is thought that they can "learn" to recognize tumors or chronic viral infections and attack more aggressively.

DNA Vaccine

Therapeutic DNA vaccines are designed to send encoded instructions to cells to render a disease-specific immune response.

DNA vaccines can hypothetically "boost" immunity when the effects of a therapeutic vaccine begin to wane, or overcome "immune exhaustion" caused when a long-time infection (such as HIV) diminishes the immune system's ability to recognize a pathogen.

Types of Therapeutic Vaccines

Although only three therapeutic vaccines have received FDA approval to date, there are others that have shown enormous promise in treating different cancers or viral infections.

Cancer

The greatest strides in therapeutic vaccine research have been in the treatment of cancer. Of the three vaccines approved for use in the United States, two are used to treat advanced metastatic disease, while the other is used to prevent the progression of carcinoma in situ (precancer).

The approved vaccines, by order of approval date, are:

Other therapeutic vaccines in development include Canvaxin (an allogeneic vaccine for invasive bladder cancer), GVAX (a whole-tumor cell vaccine for pancreatic ductal adenocarcinoma), and TroVax (an antigenic vaccine for renal cell carcinoma).

HIV

There are no therapeutic vaccines approved for the treatment of HIV, but encouraging results are beginning to emerge from early clinical research.

Much of the research is based on a rare subset of people known as long-term non-progressors who are able to avoid HIV disease progression despite being infected. Many of these have unique broadly-neutralizing antibodies (bnAbs) that can neutralize up to 99% of all HIV strains.

Scientists hope to replicate this effect with therapeutic vaccines, leading to a functional cure for HIV (in which the infection remains but without symptoms or disease progression). The vaccines may also help overcome immune exhaustion in people on antiretroviral therapy who are unable to achieve immune recovery.

Herpes Simplex Virus

Herpes simplex virus (HSV) is also being explored in therapeutic vaccine research. Because scientists understand more about why the dormant virus will suddenly reactivate and cause herpes outbreaks, research has been focused on creating a vaccine that can continually suppress the virus without the use of antiviral drugs.

If successful, therapeutic HSV vaccines will reduce viral shedding, a phenomenon in which the virus will suddenly replicate, increasing the concentration of viruses in tissues and bodily fluids. Shedding not only intensifies during an acute herpes outbreak but also increases the risk of transmission to others.

Several vaccine candidates have shown promise in reducing HSV shedding and lesions in early research, including:

  • HSV529, a vaccine utilizing a replication-defective virus that can induce a stable antibody response without causing disease
  • Delta gD-2, a vaccine utilizing a genetically altered herpes virus
  • GSK4108771A, a novel vaccine that uses messenger RNA (mRNA) technology that enabled the development of the Moderna and Pfizer COVID-19 vaccines

Human Papillomavirus (HPV)

Vaccine researchers are looking for ways to improve the clearance of human papillomavirus (HPV) from the body after infection. Although clearance of the virus occurs on its own in the majority of cases, there are some in whom the infection will persist and lead to cervical cancer, anal cancer, and other types of cancers in later life.

While there are vaccines that can prevent HPV, there are none that can treat HPV infection after it has occurred. Finding one is considered imperative given that 90% of men and women in the United States will be exposed to HPV at some point in their lives.

Research into the development of therapeutic HPV vaccines often overlaps with that of targeted cancer therapies. This is because many of the vaccine candidates aren't designed to attack the virus but rather the tumors caused by the virus.

Among some of the HPV candidates currently under investigation are:

  • Candin, a vaccine candidate used for those with high-grade intraepithelial lesions associated with the development of cancer
  • Hespecta, a vaccine candidate used to treat tumors caused by HPV 16 (a high-risk strain of the virus)
  • SLP-HPV-01, a synthetic vaccine used to treat pre-malignant tumors in HIV-positive men with anal cancer

Hepatitis B

Because there are no curative treatments for hepatitis B (unlike those used for hepatitis C), therapeutic vaccines are seen as a way to slow the progression of a disease that can cause cirrhosis, liver failure, and liver cancer in some.

By stimulating the appropriate immune response, a vaccine may be able to reduce the hepatitis B viral load (the measure of viral activity). A high viral load correlates to faster disease progression.

Some of the more promising therapeutic vaccine candidates for hepatitis B are:

  • GS-4774, an antigen vaccine that includes yeast-based adjuvant (a substance that induces a more robust immune response)
  • HBsAg-HBIG, another antigen vaccine that contains an aluminum-based adjuvant
  • HBsAg/HBcAg, an antigen vaccine that combined two different hepatitis antigens (one from the surface of the virus and one from the core)

A Word From Verywell

Therapeutic vaccines are an exciting field of vaccine research. With three FDA-approved vaccines serving as its proof of concept, the field is likely to expand as scientists learn more about the mechanisms that cause disease progression. By blocking these mechanisms, the disease is not "cured" per se but may be far less able to cause illness.

Despite the enthusiasm surrounding therapeutic vaccines, it is still a nascent field of research, and it will be likely years before we see an effective one for viral diseases like HIV, hepatitis B, or HPV. Until then, it is important to focus on prevention to avoid getting these potentially serious infections.

Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Gulley JL. The ultimate personalized therapy? Hum Vaccin Immunother. 2013 Jan 1;9(1):219-21. doi:10.4161/hv.22106

  2. Parmiani G, Pilla L, Maccalli C, Russo V. Autologous versus allogeneic cell-based vaccines? Cancer J. 2011 Sep-Oct;17(5):331-6. doi:10.1097/PPO.0b013e3182337a76

  3. Wang XY, Wang B, Wen YM. From therapeutic antibodies to immune complex vaccines. NPJ Vaccines. 2019;4:2. doi:10.1038/s41541-018-0095-z

  4. Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, Buonaguro L. Antigen-specific vaccines for cancer treatment. Hum Vaccin Immunother. 2014 Nov;10(11):3332-46. doi:10.4161/21645515.2014.973317

  5. Mastelic-Gavillet B, Balint K, Boudousquie C, Gannon PO, Kandalaft LE. Dendritic cell vaccines—recent breakthroughs and encouraging clinical results. Front Immunol. 2019;10:766. doi:10.3389/fimmu.2019.00766

  6. Cheng MA, Farmer E, Huang C, Lin J, Hung CF, Wu TC. Therapeutic DNA vaccines for human papillomavirus and associated diseases. Hum Gene Ther. 2018 Sep;29(9):971-96. doi:10.1089/hum.2017.197

  7. Organon Teknika. Package insert - Tice. Updated February 2009.

  8. Dendreon Pharmaceuticals. Package insert - Provenge. Updated July 2017.

  9. Amgen. Package insert - Imlygic. Updated October 2015.

  10. Jou J, Harrington KJ, Zocca MB, Ehrnrooth E, Cohen EEW. The changing landscape of therapeutic cancer vaccines-novel platforms and neoantigen identification. Clin Cancer Res. 2021 Feb 1;27(3):689-703. doi:10.1158/1078-0432.CCR-20-0245

  11. Mylvaganam GH, Silvestri G, Amara RR. HIV therapeutic vaccines: moving towards a functional cure. Curr Opin Immunol. 2015;35:1-8. doi:10.1016/j.coi.2015.05.001

  12. Dropulic LK, Oestreich MC, Pietz HL, et al. A randomized, double-blinded, placebo-controlled, phase 1 study of a replication-defective herpes simplex virus (HSV) type 2 vaccine, HSV529, in adults with or without HSV infection. J Infect Dis. 2019 Aug 9;220(6):990-1000. doi:10.1093/infdis/jiz225

  13. Hook LM, Awasthi S, Dubin J, Flechtner J, Long D, Friedman HM. A trivalent gC2/gD2/gE2 vaccine for herpes simplex virus generates antibody responses that block immune evasion domains on gC2 better than natural infection. Vaccine. 2019 Jan 21;37(4):664-9. doi:10.1016/j.vaccine.2018.11.076

  14. ClinicalTrials.gov. A study on the reactogenicity, safety and immune response of a vaccine against herpes simplex virus (HSV)-2 in healthy participants aged 18-40 years. Updated March 18, 2021.

  15. Morrow MP, Yan J, Sardesai NY. Human papillomavirus therapeutic vaccines: targeting viral antigens as immunotherapy for precancerous disease and cancer. Expert Rev Vaccines. 2013 Mar;12(3):271-83. doi:10.1586/erv.13.23

  16. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2018. Updated October 7, 2019.

  17. Rumsfield CS, Roller N, Pellom ST, Schlom J, Jochems C. Therapeutic vaccines for HPV-associated malignancies. Immunotargets Ther. 2020;9:167-200. doi:10.2147/ITT.S273327

  18. Al-Mahtab M, Akbar SMF, Aguilar JC, et al. Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis BHepatol Int. 2013;7:981-9. doi:10.1007/s12072-013-9486-4