Why is there no toxoplasmosis vaccine?

Question

I assume there is some misunderstanding on my part about the vaccine-creation-process and which factors play a role in it. Below is my current understanding.

About toxoplasmosis:

Toxoplasmosis is a disease that can infect both humans and cats. It doesn't have a lot of symptoms, i.e. if you have it, you might not even notice. After you have had it, you are immune to further infection because your body has toxoplasmosis-antibodies now.

Toxoplasmosis is dangerous in one situation: if a pregnant woman gets it, it may cause disabilities in the baby (even at later ages when he/she grows up) or even abortion. This can only happen if the woman has not had the disease earlier in life, because then she would be immune. (It's also dangerous for people with a weakened immune system, such as hiv-patients, but you can't vaccinate them anyway so let's disregard them for this question.)

About vaccines:

Vaccines are weakened or dead virusses/microbes that cause a certain disease. The body recognises them as a threat, makes the appropriate antibodies and remembers these antibodies in case it encounters this disease again. When the non-weakened disease shows up, the body doesn't need the time to invent/create the antibodies anymore, so it can start to destroy the disease before it becomes too strong.

This only works for diseases for which your body can invent antibodies (given enough time), for which it will remember the antibodies and for which the pathogens don't evolve fast.

My question:

Why is there no toxoplasmosis-vaccine available? It seems toxoplasmosis is an ideal vaccine-candidate: the body can create antibodies and will remember them. The pathogen doesn't even need to be dead or weakened, since the symptoms for the disease are so low. It seems to me that this vaccine would be "just" inserting the toxoplasmosis-germs into the patients blood.

I'm thinking about a vaccine for women who are not pregnant. Obviously inserting toxoplasmosis into pregnant women is a bad idea.

Possibilities that I thought of:

• The toxoplasmosis is caused by a parasite, which may be too big of a difference with virusses/mirobes to create a vaccine out of? But why would that be harder?

• Toxoplasmosis may have annoying pathogens, that don't want to survive and reproduce in a lab, so you'd have to hunt the parasites down in "the wild" for every vaccine, which doesn't seem to be feasible.

• Something causes such a vaccine to be too expensive for the hasstle.

• Nobody wants to fund research to create such a vaccine, because other diseases are more dangerous.

Related question: https://health.stackexchange.com/questions/16033/why-are-some-viruses-harder-to-make-vaccines-for but this question asks for all possible reasons why a vaccine can not be created. I'm interested specifically in toxoplasmosis.

Answer 1

Short answer, loaded with opinion: Inherent difficulties present but mainly not enough resources allocated to this problem until now.

Longer version, based on other expert opinions and research results –– or really: challenges:

The reasoning in the question is indeed plausible and puzzling. It should be easy, on the face of it. Only that this pathogen is widespread and comparatively mild, making other venues seemingly more pressing. But there were attempts, illustrating some problems along the way:

Toxoplasmosis, caused by an intracellular protozoan parasite, Toxoplasma gondii, is widespread throughout the world. The disease is of major medical and veterinary importance, being a cause of congenital disease and abortion in humans and domestic animals. In addition, recently it has gained importance owing to toxoplasma encephalitis in AIDS patients. In the last few years, there has been considerable progress towards the development of a vaccine for toxoplasmosis, and a vaccine based on the live-attenuated S48 strain was developed for veterinary uses. However, this vaccine is expensive, causes side effects and has a short shelf life. Furthermore, this vaccine may revert to a pathogenic strain and, therefore, is not suitable for human use. Various experimental studies have shown that it may be possible to develop a vaccine against human toxoplasmosis. Recent progress in knowledge of the protective immune response generated by T. gondii and the current status of development of a vaccine for toxoplasmosis are highlighted.

Kur J, Holec-Gasior L, Hiszczyńska-Sawicka E.: "Current status of toxoplasmosis vaccine development.", Expert Rev Vaccines. 2009 Jun;8(6):791-808. doi: 10.1586/erv.09.27.

Even if relatively mild, introducing pathogenic elements is unethical. And may not sell that well?

Among the reasons for the difficulties encountered were:

• Lack of efficacious protective antigen candidates
• Lack of detailed understanding of pathogenic, immune and host cell invasion mechanisms
• Insufficient advanced research techniques and theories of immunology or vaccinology
• Can DNA vaccines fulfill their promise?
• Biosafety of DNA vaccines
• Immune tolerance and allergy problems of DNA vaccines
• The efficacy of DNA vaccines

Qi Liu, Lachhman Das Singla, and Huaiyu Zhou: "Vaccines against Toxoplasma gondii: Status, challenges and future directions", Hum Vaccin Immunother. 2012 Sep 1; 8(9): 1305–1308. doi: 10.4161/hv.21006

Research is not standing still on this front. Especially DNS vaccines seem to have made some progress:

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects all warm-blooded animals including humans and causes toxoplasmosis. An effective vaccine could be an ideal choice for preventing and controlling toxoplasmosis. T. gondii Superoxide dismutase (TgSOD) might participate in affecting the intracellular growth of both bradyzoite and tachyzoite forms. In the present study, the TgSOD gene was used to construct a DNA vaccine (pEGFP-SOD).

The present study revealed that the DNA vaccine triggered strong humoral and cellular immune responses, and aroused partial protective immunity against acute T. gondii infection in BALB/c mice. The collective data suggests the SOD may be a potential vaccine candidate for further development.

Yuan Liu et al.: "Immunization with a DNA vaccine encoding Toxoplasma gondii Superoxide dismutase (TgSOD) induces partial immune protection against acute toxoplasmosis in BALB/c mice", BMC Infect Dis. 2017; 17: 403. Published online 2017 Jun 7. doi: 10.1186/s12879-017-2507-5

These are promising but still quite preliminary. Whether looking at live or live-attenuated vaccines, protein vaccines, DNS vaccines, epitope vaccines, carbohydrate vaccines, exosome vaccines, RNA vaccines or possible adjuvants, a big bunch of ideas is considered, developed and tested for. Only that they really lack a base of attack.

One of the latest reviews in the field summarises it:

Despite continuous research efforts, there are still very few effective strategies against toxoplasmosis. In the past few years, numerous vaccination experiments have been performed to control T. gondii infection.

In this review, the authors summarize the development of T. gondii vaccines with proper adjuvants, ranging from live or live-attenuated vaccines to protein vaccines, DNA vaccines, epitope vaccines and novel vaccines. They also highlight the challenges involved in the development of T. gondii vaccines, including specific impediments and shortcomings.

Expert opinion: Moving towards the development of effective vaccines against T. gondii is not only a tedious mission but also a difficult challenge. Future studies should consider new approaches and strategies for vaccine development, particularly novel vaccines and genetic adjuvants, as well as optimizing immunization protocols and evaluation criteria.

Yawen Li & Huaiyu Zhou: "Moving towards improved vaccines for Toxoplasma gondii", Expert Opinion on Biological Therapy, Volume 18, 2018 - Issue 3, https://doi.org/10.1080/14712598.2018.1413086

The unsound base from which most of this research is fishing in the dark is that neither the life cycle nor the actual most of invasion/infection are fully understood. Not in the least because there are quite a few strains in the wild, some much more pathogenic than others.

The last cited review opinion closes with:

In our view, directions for future research should focus on the development of an effective cat vaccine. Such a vaccine would prevent oocyst shedding by cats and reduce oocyst contamination of the environment and risk to animals and humans. The priority is to develop a live-attenuated vaccine using non-reverting mutants. With the wide use of CRISPR technology, generating gene deletion mutants as live vaccines has become feasible and provides a novel approach for the control of toxoplasmosis. Therefore, it is expected that several years will be required before an effective vaccine against T. gondii is ready and available.