The Future of Vaccination: Part 1 – New Delivery Techniques & Vaccines

Vaccines have been a strong force in the global fight against infectious disease for more than 200 years. Thanks to vaccination, smallpox is gone from the world and polio is on the verge of eradication. However, the future presents us with continued challenges. Diseases such as HIV/AIDS and Malaria still do not have effective vaccines, and others are still prevalent in areas of the world where vaccines are unaffordable or there are not enough clinics and workers to deliver the vaccines. Current and future goals in vaccination include looking for vaccines with higher effectiveness, lower cost, and convenient delivery. Here are some exciting vaccination prospects and challenges that we will face in the future.

New Techniques in Vaccine Delivery

Microneedle patches

What if your yearly flu shot was a simple device that was sent to you in the mail, and you could administer it easily by yourself without the pain of a needle jab? Well, in five years from now, it could be a reality!

A new study has tested the use of a “microneedle patch” which could be used to deliver vaccines, and found the results to be quite promising. This patch consisted of 50 tiny needles, each less than 1 mm thick, arranged at the center of a thin, flexible foam pad about the size of an adult fingertip.

Prausnitz_MicroneedlePatch_Application

Participants in the study rated the pain of an intramuscular injection (needle jab into the muscle) to be 15 out of 100, while the microneedle patches were less painful, scoring 1.5 out of 100.

Besides being smaller and easier to use than the typical flu vaccine, the microneedle patch also does not need refrigeration, so it could potentially be made available for use outside of the doctor’s office or healthcare setting. Also, this means that the vaccine can be used in developing countries, where refrigeration can be a hindrance to vaccine delivery.

By using such a device, the number of patients waiting in clinics to get a flu shot could be reduced, which translate to lower healthcare costs for flu vaccination programs. More importantly, the convenience of this patch could increase flu immunisation rates, and could be used to deliver other vaccines too! Researchers plan to start a clinical trial in spring of this year, with the goal of making these patches available within 5 years.

Inhaled Vaccines: Nasal Spray

This nasal spray flu vaccine, also called ‘Live Attenuated Influenza Vaccine’ is approved for use in people from 2-49 years of age. All nasal spray flu vaccines for the 2014-2015 season provide protection against four flu viruses: an influenza A (H1N1) virus, an influenza A (H3N2) virus and two influenza B viruses.

equipnet_pharmaceutical_industry_nasal

There is evidence that the nasal spray flu vaccine may work better than a flu shot in younger children. A study showed that the nasal spray flu vaccine prevented about 50% more cases of flu than the flu shot in younger children. Therefore, the Centers for Disease Control and Prevention (CDC) now recommends the nasal spray vaccine for healthy children 2-8 years if it is immediately available.

Vaccines for Ebola

The Ebola virus was first identified in 1976. Because Ebola outbreaks were rare and past outbreaks have been controlled quickly, commercial vaccine manufacturers have not been urgent in advancing vaccines through clinical trials. That changed in 2014, when Ebola virus emerged at unprecedented levels in West Africa.


Ebola virus particles budding from African green monkey kidney cells.

Since the epidemic began in March 2014, there has been approximately 25 000 cases, and more than 10 000 deaths from the disease.

In 2014, vaccines previously tested only in animals were fast-tracked into Phase 1 clinical trials. There are currently four clinical trials in process for Ebola vaccine. In fact, phase 2 and 3 vaccine trials are already being planned. Trial participants will be those at high risk of contracting the disease, such as healthcare workers and family members of infected people.

 

Vaccines for Malaria

Unlike any infectious disease for which there is already a successful vaccine, malaria is transmitted via a parasite (Plasmodium species) that passes through multiple life stages, each of which presents a unique challenge to vaccine developers. Because the parasite can reproduce both asexually (in the host’s body) and sexually (in the mosquito vector’s gut), it has many advantages over the viruses and bacteria that we currently vaccinate against. Also, infection with malaria does not confer “sterile” immunity, which means that if you get malaria and you recover, you can be infected over and over again. However, future infections will probably be less severe. This is known as naturally acquired immunity and is why malaria is deadly for anyone who has never been infected before, such as children under five or foreign travellers.

A challenge with malaria’s “naturally acquired partial immunity” is that it does not last long. In fact, if someone has lived in Africa for his or her entire life and leaves for even a year, he or she will lose this immunity and once again be as vulnerable to malaria as someone who had never been infected. So to develop a malaria vaccine, we need to understand the mechanism of partial immunity and develop a vaccine based on that principle.

malaria

Basic life cycle of the Plasmodium species.

Because the parasite has three different life stages, there are three vaccine approaches currently being researched.

  • Pre-erythrocytic vaccines aim either to prevent the parasites from getting into the liver cells or to destroy infected liver cells. The greatest challenge for a pre-erythrocytic vaccine is the time frame, because the parasites reach the liver less than an hour after being injected by the mosquito. Therefore, the immune system does not have time to eliminate the parasite. One vaccine, the RTS,S vaccine, is currently in Phase III trials and is showing promise, with the latest results showing a 33-50% decrease in risk of malaria in children from 6 weeks to 17 months old.
  • Erythrocytic vaccines aim to stop the rapid invasion and asexual reproduction of the parasite in the red blood cells. Most of these vaccines are still undergoing Phase I or II trials.
  • Transmission blocking vaccines target the stage of sexual reproduction that occurs in the mosquito gut. They aim to kill the Anopheles mosquito vector, to stop further spread of the parasite.

These individual stage vaccines must show efficacy on their own before scientists can develop a vaccine combining multiple approaches, which many say is the next step. Although great progress has been made, vaccine development for malaria will continue to be an expensive and multidimensional effort.

Vaccines for HIV/AIDS

Human Immunodeficiency Virus (HIV) is a major global health concern not only because it can’t yet be prevented through vaccination, but also because infection is for life and the virus targets the immune system, infecting and killing CD4+ T-cells, making the infected more prone to other infections. (when the CD4+ T-cell count drops below a certain number).

While anti-retroviral treatments have greatly improved life expectancy and quality of life for people living with HIV, preventing HIV infection is still a primary goal, especially for developing countries that are hit hardest by the pandemic and cannot afford treatment. However, HIV has unique challenges that hinder vaccine development:

  • Lack of natural immunity to HIV – Since HIV infection is for life, researchers do not have a way to identify an immune response that would be effective against HIV.
  • Variability of HIV types – HIV mutates frequently plus many different subtypes of HIV exist.
  • Lack of correlates of protective immunity – Because no infected person has been able to naturally clear the virus, scientists do not know what protection from HIV would look like in a person in terms of antibody production and T-cells required for elimination of the virus.
  • No animal model that reliably predicts vaccine efficacy in humans

Some individuals are naturally able to prevent HIV from progressing to AIDS. Research into these individuals, known as the “elite controllers”, may help HIV vaccine development. Researchers are also looking into ways of generating antibodies against HIV. Studies have shown that some humans can produce antibodies capable of neutralising a wide range of HIV strains.  These antibodies provide an excellent target for vaccine discovery by highlighting weaknesses on the surface of the virus.

Cancer Vaccines

Just as our immune systems work to protect us from harmful viruses and bacteria, they also play a role in protect us from developing cancer. We already know that the hepatitis B vaccine can help prevent us from getting hepatitis B-induced liver cancer, and the human papillomavirus (HPV) vaccine can help to prevent the majority of cervical cancers.

But what if the cancer has already appeared?

The type of vaccine that is being designed to treat cancer is called a therapeutic cancer vaccine. There are two main types of these vaccines: autologous vaccines and allogeneic vaccines. Autologous vaccines use cells from a person’s tumour to make the vaccine, whereas allogeneic vaccines use laboratory grown donor cells. For this post, we will only discuss examples of some autologous vaccines. You can find more information about cancer vaccines here.

To make an autologous cancer cell cancer vaccine, cells from a person’s tumour are removed and treated in a way that makes them a target for the immune system. They are then injected into the body, where immune cells recognise them, attack them, and then do the same to other cancer cells in the body. The idea is that memory immune cells would be generated and be able to respond if cancer cells returned in the future. Several Phase 2 and Phase 3 trials of such autologous cancer cell vaccines are in process or have been completed, but none have been licensed yet.

Another approach to autologous cancer vaccines is to use a person’s own immune cells to make the vaccine. The immune cells are extracted from the blood and exposed to a tumour antigen, stimulated and then injected back into the body. The treated immune cells should then respond to the cancer cells expressing the target antigen. There is one autologous vaccine made from immune cells that is licensed in the US. Sipuleucel-t (Provenge®) is a prostate cancer vaccine. It has been shown in clinical trials to extend life for men with treatment-resistant metastatic prostate cancer.

The cancers that are the best candidates for vaccine therapy are those whose treatments are expensive, less effective, or involve the risk of serious side effects. For example, lung cancer, pancreatic cancer, and breast cancer are such candidates for vaccine therapy. Development of vaccines to treat cancer is certainly an exciting prospect. Future research and the results of clinical trials to be announced will provide us with more weapons in our fight against cancer.

Text References

Centers for Disease Control and Prevention (CDC) (US). Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine) [Internet]. Atlanta (GA): CDC; 2014 Aug [updated 2014 Sep 9; cited 2015 Apr 7]. Available from: http://www.cdc.gov/flu/about/qa/nasalspray.htm

National Institute of Biomedical Imaging and Bioengineering (US). DIY Vaccination: Microneedle Patch May Boost Immunization Rate, Reduce Medical Costs [Internet]. Bethesda (MD): U.S. Department of Health & Human Services, National Institutes of Health; 2014 Mar [cited 2015 Apr 7]. Available from: http://www.nibib.nih.gov/news-events/newsroom/diy-vaccination-microneedle-patch-may-boost-immunization-rate-reduce-medical

The College of Physicians of Philadelphia (US). Cancer Vaccines and Immunotherapy [Internet]. Philadelphia (PA): The College of Physicians of Philadelphia; 2014 Aug [cited 2015 Apr 7]. Available from: http://www.historyofvaccines.org/content/articles/cancer-vaccines-and-immunotherapy

The College of Physicians of Philadelphia (US). Ebola Virus Disease and Ebola Vaccines [Internet]. Philadelphia (PA): The College of Physicians of Philadelphia; 2014 Oct [cited 2015 Apr 7]. Available from: http://www.historyofvaccines.org/content/articles/ebola-virus-disease-and-ebola-vaccines

The College of Physicians of Philadelphia (US). Malaria and Malaria Vaccine Candidates [Internet]. Philadelphia (PA): The College of Physicians of Philadelphia; 2014 Jul [cited 2015 Apr 7]. Available from: http://www.historyofvaccines.org/content/articles/malaria-and-malaria-vaccine-candidates

The College of Physicians of Philadelphia (US). The Development of HIV Vaccines [Internet]. Philadelphia (PA): The College of Physicians of Philadelphia; 2014 Jul [cited 2015 Apr 7]. Available from: http://www.historyofvaccines.org/content/articles/development-hiv-vaccines

The College of Physicians of Philadelphia (US). The Future of Immunization [Internet]. Philadelphia (PA): The College of Physicians of Philadelphia; 2014 Jul [cited 2015 Apr 7]. Available from: http://www.historyofvaccines.org/content/articles/future-immunization

Image References

CDC/NIAID. Ebola Virus Disease and Ebola Vaccines [Internet]. Philadelphia (PA): The College of Physicians of Philadelphia; 2014 [cited 2015 Apr 7]. [Figure], Ebola virus particles budding from African green monkey kidney cells. Available from: http://www.historyofvaccines.org/content/articles/ebola-virus-disease-and-ebola-vaccines

EquipNet News. Researchers See Promise In Nasal Vaccines [Internet]. Canton (MA): EquipNet; 2011 [cited 2015 Apr 7]. [Figure], Nasal Vaccine. Available from: http://blog.equipnet.com/2011/04/19/researchers-see-promise-in-nasal-vaccines/

Meek, G. DIY Vaccination: Microneedle Patch May Boost Immunization Rate, Reduce Medical Costs [Internet]. Bethesda (MD): U.S. Department of Health & Human Services, National Institute of Biomedical Imaging and Bioengineering; 2014 [cited 2015 Apr 7]. [Figure], Four photos showing how to apply a microneedle patch. Available from: http://www.nibib.nih.gov/news-events/newsroom/diy-vaccination-microneedle-patch-may-boost-immunization-rate-reduce-medical

Michalakis Y, Renaud F. Malaria: Evolution in vector control. Nature [Internet]. 2009 [cited 2015 Apr 7];462(7271):298-300. Figure 1, Basic features of the Plasmodium life cycle. Available from: Nature Publishing Group

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