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).

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.

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:

• Tice (Bacillus Calmette-Guerin) is a live-attenuated vaccine approved in 1990 for the treatment of carcinoma in situ of the bladder.
• Provenge (sipuleucel-T) is a dendritic cell-based vaccine approved in 2010 that is used for the treatment of metastatic, hormone-resistant prostate cancer.
• Imlygic (talimogene laherparepvec) is a live-attenuated vaccine approved in 2015 that is indicated for the treatment of advanced oncolytic melanoma.

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.

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.