Vaccines are one of the most successful and cost-effective public health interventions, which help preventing over 2 million deaths every year.

The World Health Organization (WHO) defines vaccines as:

“A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies. Vaccines include, for example, suspensions of killed or attenuated microorganisms, or products or derivatives of microorganisms. The most common method of administering vaccines is by injection, but some are given by mouth or nasal spray.”

Types of Vaccines:

As per the ‘National Institute of Health (NIH)’ of USA, following are some types of vaccines that researchers usually work on:

• Live, attenuated vaccines
• Inactivated vaccines
• Subunit vaccines
• Toxoid vaccines
• Conjugate vaccines
• DNA vaccines
• Recombinant vector vaccines

The first vaccine:

In 1796, Edward Anthony Jenner not only discovered the process of vaccination, alongside developed the first vaccine of the world for mankind – smallpox vaccine. To develop this vaccine Jenner acted upon the observation that milkmaids who caught the cowpox virus did not catch smallpox.

As per published data prior to his discovery the mortality rate for smallpox was as high as up to 35%. Thus, Jenner is very often referred to as the “Father of Immunology”, whose pioneering work has “saved more lives than the work of any other person.”

Later on in 1901 Emil Von Behring received the first Nobel Prize (ever) for discovering Diphtheria serum therapy.

The future scope of vaccines:

The future scope of vaccines is immense as several potentially preventable diseases, as indicated below remain still unaddressed.

Source: Deutsche Bank Report 

Expanded focus for vaccines:

The focus of the global vaccine industry also has been expanded from prophylactic vaccination for communicable disease (e.g. DTP vaccine) to therapeutic vaccines (e.g. Anti-cancer vaccines) and then possibly non-communicable disease vaccines (e.g. vaccines for coronary artery disease).

The Issues and Challenges:

To produce a safe and effective marketable vaccine, it takes reportedly around 12 to 15 years of painstaking research and development process involving an investment ranging between US $500 million and over $1 billion dollars (Ibid, 7).

Moreover, one will need to realize that the actual cost of vaccines will always go much beyond their R&D expenses. This is mainly because of dedicated and highly specialized manufacturing facilities required for mass-scale production of vaccines and then for the distribution of the same mostly using cold-chains.

Around 60% of the production costs for vaccines are fixed in nature (National Health Policy Forum. 25. January 2006:14). Thus such products will need to have a decent market size to be profitable.

Unlike many other medications for chronic ailments, which need to be taken for a long duration, vaccines are administered for a limited number of times, restricting their business potential.

Thus, the long lead time required for the ‘mind to market’ process for vaccine development together with high cost involved in their clinical trials/marketing approval process, special bulk/institutional purchase price and limited demand through retail outlets, restrict the research and development initiatives for vaccines, unlike many other pharmaceutical products.

Besides, even the newer vaccines will be required mostly for the diseases of the poor, like Malaria, Tuberculosis, HIV and ‘Non Communicable Diseases (NCDs)’ in the developing countries, which may not necessarily guarantee a decent return on investments for vaccines, unlike many other newer drugs. As a result, the key issue for developing a right type of newer vaccine will continue to be a matter of pure economics.

A great initiative called GAVI: 

Around 23 million children of the developing countries are still denied of important and life-saving vaccines, which otherwise come rather easily to the children of the developed nations of the world.

To resolve this inequity in January 2000, the Global Alliance for Vaccines and Immunization (GAVI) was formed. This initiative was mainly aimed at generating sufficient fund to ensure availability of vaccines for children living in the 70 poorest countries of the world.

The GAVI Alliance has been instrumental in improving access to six common infant vaccines, including those for hepatitis B and yellow fever. GAVI is also working to introduce pneumococcal, rotavirus, human papilloma virus, meningococcal, rubella and typhoid vaccines in not too distant future.

A recent example:

As if to vindicate the above points, Reuters on December 16, 2011 reported that  “Pfizer and GlaxoSmithKline are increasing sales of cut-price pneumonia vaccine to developing countries by more than 50 percent, marking the scale-up of an international program to protect millions of children.

GAVI is buying an additional 180 million doses of Pfizer’s pneumococcal vaccine Prevenar 13 and a similar quantity of GSK’s Synflorix at a deeply discounted price of US $3.50 a shot.”

Success with vaccines in disease prevention:

Source: Ehreth Vaccine 21:4105-4117

Development of vaccines through the passage of time:

Current trend in vaccine development:

Malarial Vaccine:

Reuters on December 20, 2011 reported that an experimental malaria vaccine has been developed by the British scientists, which has the potential to neutralize all strains of the most deadly species of malaria parasite.

In October 2011, the data published for a large clinical trial conducted in Africa by GlaxoSmithKline on their experimental malaria vaccine revealed that the risk of children getting malaria had halved with this vaccine. Reuters also reported that other teams of researchers around the world are now working on different approaches to develop a malaria vaccine.

Tuberculosis vaccines:

On August 11, 2011, Aeras and the Oxford-Emergent Tuberculosis Consortium (OETC) announced with a ‘Press Release’ the commencement of a Phase IIb ‘proof-of-concept efficacy trial’ of a new investigational tuberculosis (TB) vaccine. OETC indicated that clinical trial for the drug will be undertaken by them in Senegal and South Africa with primary funding support from the European and Developing Countries Clinical Trials Partnership (EDCTP).

Cancer vaccines:

Cancer vaccines are, in fact, biological response modifiers, which work by stimulating or restoring the ability of the immune system to fight the disease. There are two broad types of cancer vaccines:

• Preventive vaccines:  To prevent cancer in healthy people
• Therapeutic vaccines:  To treat cancer by strengthening the natural defense mechanism of the human body against the disease.

The United States Food and Drug Administration (US-FDA) has approved the following cancer vaccines, which protect against two types of HPV that cause approximately 70% of all cases of cervical cancer globally:

• Gardasil of Merck & Company
• Cervarix of  GlaxoSmithKline

The US FDA has also approved a cancer preventive vaccine that protects against HBV infection, which can cause liver cancer. It has been reported that the original HBV vaccine was approved in 1981 and currently most children in the US are vaccinated against HBV after their birth.

In addition, the US regulator has also approved a cancer vaccine for treatment of certain types of metastatic prostate cancer.

HIV Vaccines:

‘The AIDS Vaccine 2011 conference’ held in Bangkok in the month of September, 2011 discussed some of the latest findings on the following two vaccines for prevention and control of HIV disease progression:

• A large trial of RV 144 vaccine in Thailand demonstrated the proof of concept that a preventive vaccine with a risk reduction of 31% could effectively work.  The trial was supported by the World Health Organization (WHO) and UNAIDS.
• Bionor Pharma announced that clinical trial participants who received Vacc-4x “experienced a 70% viral load decrease relative to their level before starting Anti-Retroviral Therapy (ART), compared with no notable reduction among placebo recipients.”

Promising ‘Therapeutic Vaccines’ undergoing clinical trial:

‘FierceVaccines’ in its October 27, 2011 reported the following 10 most promising therapeutic vaccines, which are now undergoing clinical trials on humans:

Future scope for cancer vaccines:

One school of scientists firmly believes that out of all cancers diagnosed each year globally, various types of microbes contribute 15% to 25% as a causative factor for this dreaded disease, as indicated below:

Source: The International Agency for Research on Cancer (IARC)

These findings open the doors of unique opportunities to develop both preventive and therapeutic vaccines to address the life threatening near fatal ailment of mankind – cancer.

Conclusion:

Developing countries of the world are now demanding more of those vaccines, which no longer feature in the immunization schedules of the developed nations. Thus to supply these vaccines at low cost will be a challenge, especially for the global vaccine manufacturers, unless the low margins get well compensated by high institutional demand.

To effectively focus on all important disease prevention initiatives, there is also a need to build a vibrant vaccine business sector in India. To achieve these dual objectives the government should create an enabling ecosystem for the vaccine manufacturers, academics and the government funded vaccine R&D centers to concentrate more with the relevant vaccine development projects ensuring a decent return on investments, for long term public health interest.

More often than not, the above stakeholders find it difficult to deploy sufficient fund to take their vaccine projects successfully through various stages of clinical development to obtain marketing approval from the drug regulator, working out a decent return on investments. This critical issue needs to be appropriately and urgently addressed by the Government to make the disease prevention initiatives in the country sustainable, demonstrating to all concerned that disease ‘prevention is better than cure’.

By: Tapan J Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.