Since human beings stopped being hunter-gatherers and settled into agricultural communities, disease has been mankind’s harshest enemy. To counter this, the search for inoculation-based cures where a small quantity or a less virulent form of a disease-causing germ is introduced into a person’s body to build immunity goes back centuries. Evidence of such treatments was available well before Edward Jenner used the theory to develop a smallpox vaccine in the 18th century. 

Currently,  the World Health Organization (WHO) estimates that vaccines prevent an estimated 3.5-5 million deaths every year and are available for more than 20 life-threatening diseases. They combat the spread of pandemic diseases, such as flu and SARS, and are being formulated to tackle antimicrobial resistance.

As described by Dr. Princess Nothemba Simelela, Assistant Director-General, Special Advisor to the Director-General, Strategic Priorities, WHO, vaccinations are one of the greatest life-saving public health interventions in history.

 

Notable present-day innovations

An exciting development of the previous decade in the field of vaccines is the use of nanoparticles as carriers for vaccines. Nano carrier-based delivery systems offer increased protection against premature degradation, and good stability, and act as adjuvants to elicit an improved immune response. This makes the vaccine more resilient, allowing researchers to explore varied routes of administration.

Inorganic and polymeric nanoparticles, virus-like particles (VLPs), liposomes, Lipid Nanoparticles (e.g. SLN, LNP etc.) and self-assembled protein nanoparticles have all been tested as potential vaccine carriers. Gold, carbon, and silica nanoparticles have been successfully used to deliver viral antigens.

There are now more than ten covid-19 vaccines under development using miRNA and protein based nanoparticles platform which also uses liposomes/lipid nanoparticles for vaccine delivery, to tackle all past and future variants of the Sar-CoV-2 virus

 

The drivers of innovation

The history of vaccines has been one of innovation. The scientific community has had to race against an increasing number of pathogens that are evolving to destroy human lives. Pathogens already present amongst us frequently transform to evade our innate and external defenses. In addition, scientists estimate that more than 1.7 million unknown viruses exist in animals worldwide, and 38 to 50% of them could spread to humans. Phenomena such as climate change and rapid urbanization hasten this juggernaut.

Also, a vaccine needs to fulfill many other parameters to safeguard against disease effectively. A vaccine should be compatible with being manufactured at scale, transported across global supply chains, and available in variants that provide immunity against different forms of the pathogen and are safe for people belonging to different demographics. A vaccine safe for a healthy adult may not be so for a young child or an elderly individual.

This complex combination of factors that could make a difference between life and death has spurred the scientific community to continually innovate.

 

A brief history of vaccine development

It was towards the end of the 20th century that vaccinations had either eradicated or reduced mortality for a great number of diseases. Vaccine innovation and usage increased over the years and followed scientific and political-economic developments.

With modern scientific advancements, vaccines have become more sophisticated and scientists around the world are achieving breakthroughs far more often.

 

Vaccine technology evolution:

The first generation

•  Live attenuated vaccines (also called attenuated or weakened) are one of the oldest forms of vaccines. They contain weakened forms of the infectious agent that stimulate your immune system to develop immunity against that agent; live attenuated vaccines may be given by mouth or by injection into the muscle. An example is the MMR (measles-mumps-rubella) vaccine
•  Inactivated vaccines (also called killed) do not contain any living organism but rather a killed version of the pathogen that stimulates your immune system to develop immunity. It can be given only subcutaneously (under the skin), intramuscularly (into the muscle), intradermally (into layers beneath the skin), or intralesionally (into tissue directly). Polio and influenza vaccines are inactivated.

 

The second generation

–  Toxoid vaccines use toxins created by the pathogen to create immunity to the specific parts of the pathogen that causes the disease. These were introduced in the early 1900s and include vaccines for tetanus and diphtheria.

• There are also subunit, recombinant, conjugate, and polysaccharide vaccines that use particular parts of the germ or virus. These were first used in the mid-19080s. They trigger very strong immune responses in the body, making it the perfect vaccine for people who should not receive “live” vaccines, such as young children, older people, and immunocompromised people. The hepatitis B vaccine is an example.

 

The third generation

– Viral vector vaccines modify another harmless virus and use it as a vector to deliver instructions to protect us from the intended virus. Described as a gene delivery system they trigger a strong immune response. AstraZeneca’s COVID-19 vaccine is an example.

•   mRNAvaccines are ‘futuristic’ vaccines that can be developed quickly using the pathogen’s genetic code. They work by triggering an immune response from proteins they synthesize and induce both cellular and humoral immunity, such as the Pfizer-BioNTech COVID-19 vaccine.

• DNA and recombinant vector vaccines – Recombinant DNA technology involves splicing together strands of DNA from different sources (such as bacteria or viruses) so that they produce proteins that can be used for testing purposes.  Although DNA-based vaccines have not yet been approved for use in the general public, several ongoing human clinical trials on DNA vaccines are underway. One of the first clinical trials investigated the possible therapeutic and prophylactic effects of a DNA vaccine against HIV.

 

The role of patents

Given the time, money, and effort that goes into making vaccines, patents ensure certain much-needed parameters are followed across the ecosystem – such as recognizing innovation and ensuring the high standards that are crucial for a life-saving product.

Patents also reward the patent owner which is often a large corporation with exclusive and substantial profits, at least in the initial years of vaccine manufacturing. And this has always been a subject of contention.

While patent supporters believe in limiting access to intellectual property to ensure innovations are cutting-edge and profitable, justice for the less fortunate is also an important argument. While profit provides the impetus to innovate and boost production, basic human rights should not have to play second fiddle, especially in health emergencies.

 

During the pandemic

As expected, this debate was pushed to the forefront during COVID-19 with some countries such as the US and India, and the World Trade Organization (WTO) arguing for the suspension of intellectual property rights related to COVID-19 vaccines, medicines, and technologies, and the EU countries and the pharma companies opposing it.

In the wake of COVID, several companies came together for ‘The Open Covid Pledge’, which hands out “non-exclusive and royalty-free” licenses for Covid products. They provide an open framework under which patent holders can voluntarily pledge not to assert the exclusivity of their rights to manufacture, use, sell, reproduce and import these products. 

A partial waiver of Covid-19 vaccine patents benefiting developing countries also came through in June 2022. But this might be too little, too late. Production of Covid-19 vaccines has increased dueto the demanding global markets.Also, manufacturing vaccines of the required quality needs much more than the lifting of patents. Technology transfer, advanced infrastructure, and the right supply chain are just some of the variables that need to fall into place.

Meanwhile,  two scientists Peter Hotez and Maria Elena Botazzi, co-directors of the Center for Vaccine Development at Texas Children’s Hospital, invented a safe, easy-to-make vaccine and kept it patent-free. India was quick to leverage its existing infrastructure to manufacture the jab known as Corbevax, and by August 2022, 70 million doses had been given to adolescents in the country.

 

What lies ahead?

Currently, there are several frameworks in place regulating patents and ownership rights.

The World Trade Organization’s Trade-Related Aspects of Intellectual Property Rights agreement is one such framework.  It obliges all WTO member states to offer 20 years of monopoly protection on new patented products. Although there is a group of 35 least developed WTO member states that are exempt, all the other countries have to play by these rules, making sure that if a patent holder has a patent for a country, that country cannot reverse engineer and try to develop a generic equivalent.

The two schools of thought around vaccine patents have been at odds almost since the beginning of mass vaccinations. Jonas Salk who led the team that developed one of the first polio vaccines famously said “Could you patent the sun?”. Salk believed the vaccine belonged to the people.

He was right as, in this instance, the public had funded the development process by the National Foundation for Infantile Paralysis which was itself a non-profit. So there was an almost universal consensus that the vaccine was already paid for.

Interestingly, towards the end of his illustrious career, Salk helped set up a corporation to develop an HIV vaccine. Though the outcome was unsuccessful, Salk’s company moved to patent the vaccine in the initial stages.

The hunt for an answer continues. Government funding, patent pools, domestic patent laws, cash rewards for new vaccines, transfer of technology from advanced countries, and global initiatives to foster innovation are just some ways to ensure vaccines reach the largest possible section of humanity while maintaining the highest possible scientific and regulatory standards.

 

Highlights about Researchwire’s Forte in this domain:

The pharma and life science team had worked on several projects in the past related to various aspects of vaccine innovation like vaccine formulation, vaccine compositions and vaccine development. The team had handled vaccine related projects for the aquatic animals, poultry, swine, and human use.

In the current context, the most important work done by the team was related to Lipid Nanoparticles and Liposome formulation for the drug delivery especially in the development of vaccine against Covid-19 virus. The work comprises exploration of various LNP and Liposome formulations, manufacturing technologies, finding various LNP/Liposome Based Therapeutics in Market, key ingredients of LNP/Liposomes, their suppliers and manufacturers, propriety manufacturing technology owners and their associations/alignments with pharma/biotech players. Amongst the various technologies’ aspect for vaccine innovation, the team also did perform in depth review of microfluidic device for the continuous production of lipid nanoparticles/ liposomes/ polymeric nanoparticles.

The other similar works (related to nanomaterials) are Liposomal Cisplatin and Platinum based drugs and Exosomes based Wound Dressing Materials.

 

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