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Source: The updated

Attractive unconventional indications for vaccines developers

Source: The updated

Source: An updated graph from the “Active immunization for unconventional indications” Report on www.martinalutter.com

It is interesting to have a look on activities of drug developers in area of antibody-inducing vaccines directed against non-infectious diseases and some unconventional indications. These vaccines have been in most cases developed so far as treatment vaccines. This is in opposite to infectious diseases vaccines used as prophylactic vaccines. Despite promising late stage candidates, with some very recent failures, there is still no antibody-inducing vaccine approved targeting other than microorganism antigens (i.e targeting self antigens, addiction molecules antigens and others).

As is also observed in other drug development areas, most of the vaccines are focused on different cancer types and among these, predominantly on solid cancers. Here prostate and breast cancer attracted the most attention of vaccine developers, followed by pancreatic, melanoma, non-small cell lung cancer (NSCLC) and colorectal cancer. There are some vaccines which are tested in clinical trials for multiple cancer indications.

The second most developed area is that of vaccines against neurodegenerative diseases, predominantly against Alzheimer’s disease. Despite a lot of immunotherapy (including mAbs and plasma infusions) failures in recent years there are still more than 10 vaccines in active development against Alzheimer´s disease, targeting one of two main molecules thought to be involved- Aβ and Tau. And, there are some other specialties here like a first ever vaccine for Parkinson´s disease targeting α-syn or a vaccine against Huntington’s disease or Multiple system atrophy.

The third most active development is in allergy indications. Most of the vaccine efforts are still focusing on allergen specific vaccines, though the approach is different from the whole allergen hyposensibilization. There are however also attempts to have a general IgE vaccine to be used in all allergies and IgE-related diseases.

Interestingly, people believe that vaccines can help also with different human addictions– for smoking cessation and drug abuse, as is seen from the fairly high number of vaccines in development for these indications. There have been some failures, especially in smoking cessation efforts, however, there are still some vaccines for this indication in development.

Cardiovascular diseases attract the attention of all drug developers. This is no different in the area of vaccine development. Principally there are vaccines in development aiming at treating hypercholesterolemia and hypertension. It will be interesting to observe the fate of the cholesterol-lowering vaccines in the light of recent findings showing no significant effect of the reduction of “bad” cholesterol, induced in that case by a small molecule targeting CETP, on cardiovascular diseases rate.

The 6th most popular area with a lot of activity in vaccine development has been autoimmune disorders. However, there are more stopped vaccine projects than projects in active development at the present time.

All in all, out of 188 vaccines in the report “Active immunization for unconventional indications”, 97 is still as of today in active development.

There were discontinuations of some late stage candidates in recent weeks.

The aim of the above mentioned report is to provide information about vaccines in development for unconventional indications and non-infectious diseases. Further focus is placed on sophisticated antigen(s)-specific vaccines and vaccines where induced polyclonal antibodies are claimed to be the main mode of action. The scope of this report does not include vaccines against microorganisms which are used for non-infectious diseases (e.g. cancer vaccines targeting HPV). Also, the term “vaccine” as used in this report does not mean a monoclonal antibody (mAb) or immunoglobulin (IgGs) infusion.

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Vaccines for non-infectious diseases?

Who is developing antibody-inducing vaccines for unconventional indications like different chronic diseases, addictions, autoimmune and genetic diseases? Are there vaccines which cure or prevent cancer, Alzheimer´s diseaseParkinson´s disease or Huntington´s disease? Can we decrease high cholesterol and prevent cardiovascular diseases by a vaccine? Can be a cocaine addiction treated by a vaccine? Or can somebody quit smoking by a simple vaccination?

Results from which clinical trials are expected to be available this year? Which indications are the most attractive for vaccine developers? What are the strategies companies adopt for vaccines development? How to define an ideal vaccine composition which enables to induce a strong, effective and long lasting antibody response? What target is the mostly employed when we talk about antibody-inducing vaccines for unconventional indications? What are highs and falls of vaccines development? Do you want to compare target product profiles for more than 100 active vaccine candidates? Which companies and academic institutions are the most active in vaccines development for unconventional indications? What are the technologies behind? Many answers can be found in the report “Active immunization for unconventional indications”.

Vaccines are one of the most important treatments ever developed. Since 1796 when the first vaccine was tested (against smallpox), vaccines have saved millions of lives and many infectious diseases have been eradicated. This is a continuous process.

A traditional vaccine is a prophylactic vaccine which usually induces long-life immunity against exogenous or foreign antigens expressed on microorganisms. Usually, but not in all cases, these exogenous antigens induce a robust immune response where innate and specific immunity is involved. Immunization with weakened or dead microorganisms or their parts which have been made synthetically, protects against diseases caused by them.

Lessons have been learnt from infectious diseases and years ago people started to study vaccines for chronic diseases too, where a new challenge was introduced- inducing immune reaction against the own molecules which were thought to be involved in pathological processes. These own molecules could either be modified or overexpressed in the body or they could simply attain a structure which changed their function from a protective or normal one to a pathological one. What is important is that the body itself is not able to produce an adequate immune reaction to eradicate such overexpressed or modified molecules. There are successful efforts to help the immune system in chronic diseases by passive vaccination- by infusion of monoclonal antibodies. Therefore the way for using vaccines in indications such as cancer, metabolic diseases, cardiovascular diseases and other chronic diseases is laid open.

Furthermore, there are aims to use vaccines to tackle the “over” reaction of the immune system as is seen in allergic reactions. Here, instead of whole allergen hyposensitization being used, which is a long-lasting, expensive and sometimes not a very effective way to prepare an allergic person to be exposed to their allergen(s), new allergy vaccines are developed in a sophisticated way by creating synthetic vaccines with defined allergen antigens inducing an immune response shifting from IgE to IgGs production or vaccines simply targeting IgE itself.

We should not forget efforts made to use vaccines in the fields of human addictions, biological weapons and recently also in genetic diseases.

All these attempts try to use the best from a vaccine approach- a specific and long-lasting effect and the feasibility to treat a large number of the population without exhausting health insurance systems.

It needs to be said that in contrast to infectious disease vaccines, vaccines inducing antibodies and used for unconventional indications within the scope of the report are, with the exception of two of them, intended to be therapeutic vaccines. There is still a long way to go until there will be working prophylactic vaccines which could be used to protect people from diseases such as various cancers, Alzheimer’s disease, seasonal allergy, smoking addition or obesity. Results from therapeutic vaccinations along with intensive biomarker research and an in depth understanding of the etiology of diseases are paving the way for prophylactic vaccines.

The majority of vaccines for unconventional indications are in development in biotech companies and at universities.

There are however also some big pharma companies involved at the moment in active development which indicates that this approach to bring vaccines to unconventional indications has attracted attention also from big pharma players, sometimes with their own experience with vaccines against infectious diseases.

The year 2016 will be quite unique in regards to development of active vaccinations for non-traditional indications within the scope of the report– there should be results available from about 20 Phase III to Phase I trials.