Unlocking the true potential of Vaccines by Heat Stabilization

By: Hilleman Laboratories on January 11, 2018

Contributing to the high child mortality rates, rotavirus causes 0.12 million child deaths in India every year¹. In most of the developing countries rotavirus is the leading cause of diarrhea, which causes these untimely deaths².

These numbers are startling even more because diarrhea is a preventable disease, and these deaths are a result of the lack of accessibility of vaccination required for the treatment for these diseases. This problem is most prevalent in India and other developing nations like Bangladesh and few African countries.

Hilleman Laboratories is a joint-venture between Merck Sharp Dohme (MSD) and Wellcome Trust. Their mission is to make the vaccines which are affordable and of high impact to the people of developing countries with an innovative technology like heat stable vaccine for Rotavirus.

Since its inception, Hilleman Laboratories is focused on making affordable vaccines using innovation to address gaps that exist in low resource settings. It invests majority of its resources in the research and clinical assessment of vaccines against strains of diseases prevalent in the developing world bearing 90% of Global Burden of Disease.

Two-third of the children do not receive their vaccinations on time, this exposes children to this deadly disease³. Global organization like GAVI and PATH are working towards efforts of making Rotavirus vaccine more readily available in the developing countries. Hilleman Laboratories has also reinforced the Global efforts to address this problem. Hilleman Laboratories conducted the study in partnership with the International Centre for Diarrhoeal Disease Research, Bangladesh icddr,b. icddr,b works towards solving key public health problems, through innovative and scientific research, as stated in their mission. The results of the clinical trials were presented at the Vaccines for Enteric Disease Conference 2017, held in Albufeira, Portugal.

Sharing results of the study, Dr K. Zaman, Senior Scientist and Epidemiologist at icddr,b said, “Safety data have demonstrated that administration of HSRV, when compared with placebo, did not result in an increased reporting of solicited AEs in the adult cohort. In infants when administered as 3-dose primary series, HSRV had a safety profile similar to RotaTeq in terms of frequency, severity, and causality of solicited adverse effect. Immunogenicity assessment was found to be comparable between the HSRV and RotaTeq in infants. The percentage of infants exhibiting a 3-fold rise in serum anti-rotavirus IgA at 1-month post-dose 3 administration from baseline in HSRV group was 88%. The percentage of infants who had a similar increase in the RotaTeq group was 84%. In addition, HSRV elicited comparable Geometric Mean Titre relative to RotaTeq, 1 month after completion of 3-dose vaccination schedule. Based on the encouraging results obtained in this study, HSRV will be further evaluated in immunogenicity and safety studies in infants.

Hilleman Laboratories HSRV aims at simplifying the accessibility and affordability of the vaccine in the less fortunate countries, to help them in their battle against diarrhea.

Dr Davinder Gill, CEO, Hilleman Laboratories also presented his views on the same as he said, “Rotavirus is the leading cause of severe diarrhea and related deaths in children less than five years worldwide. First-generation Rotavirus vaccines possess thermostability profiles that may not need storage requirements in developing countries, highlighting need for heat stable vaccines. Considering the urgent need for effective and affordable Rotavirus vaccine, we would like to accelerate the development of our simplified, easy-to-use, heat-stable vaccine”.

The introduction of this heat-stable vaccine for Rotavirus will have a potential to change mortality, morbidity but increasing its access to geographies where it is most required.

1. http://www.huffingtonpost.in/2016/07/11/13-children-die-of-diarrhoea-every-hour-in-india-health-ministr_a_21430279/
2. http://www.who.int/bulletin/volumes/90/10/12-101873/en/
3. http://ns.umich.edu/new/releases/23958-most-kids-in-india-lack-timely-vaccinations

Read More

Vaccination: A Dot for One and Cure for Two

By: Hilleman Laboratories on November 27, 2017

The concept of vicarious learning is well known in the field of psychology. It suggests that a person can learn or unlearn a behavior just by observing the outcomes of that behavior, from someone else. That sets a good ground for the concern that would be discussed here today. We will discuss how vaccinating your child - especially when you have access to it can play a role in protecting those who do not have accessibility to these life-saving vaccines. Vaccination is a basic medical amenity, but is still a privilege for many in emerging economies.

Vaccination has shown a significant amount of reduction in many life-threatening diseases in the past few years. It is a way of making the body immune to diseases, by injecting weakened antigens (germs) of a disease such as measles or smallpox into the body. To its reaction, the body produces antibodies (protein) to fight these germs. It is a way of preparing the body to provide immunity from a disease. Moreover, vaccination is seen not only as a way of curing a disease for the one who gets vaccinated, but also for others around you, who unfortunately cannot afford this treatment with the help of Herd Immunity.

WHO published a report based on the Global Health Observatory (GHO) data in the year 2016, which stated that 5.6 million children died under the age of 5. The same sources have also reported that diarrhea is one of the most significant causes of death, along with other diseases such as malaria, measles and a few others^1,2.

In a report by Global Disease Burden, 2016, it was revealed that India alone registered deaths of 0.9 million children under the age of 5. What is more shocking is that it is the highest number globally, even more than the countries ranking below India in poverty rates³.

When a child is vaccinated, it eliminates both the risk of the disease as well as its spread. However, these vaccines are not accessible to a large part of the population, especially in developing countries like India, due to costs and maintenance factors. As a result, parents who have accessibility to these vaccines are advised to get their children vaccinated, as it cuts down on the spread rate of these diseases.

Making this happen does not seem like a distant dream now, with some organizations already working towards it. One such initiative, in this direction, is taken by an India based organization, Hilleman Laboratories. Hilleman has adopted innovative technological modes to create vaccines at much lower prices, with the technique of novel packaging. This way, the cost reduction in manufacturing will also affect the accessibility cost.

1. http://www.who.int/gho/child_health/mortality/mortality_under_five_text/en/
2. http://www.who.int/gho/child_health/mortality/causes/en/
3. http://indianexpress.com/article/india/under-five-mortality-rate-highest-in-india-report-lancet-uttar-pradesh-kerala-4845938/

Read More

How Recent Innovation in Vaccination will ‘Help Combat Cholera in Present & Future Times’

By: Hilleman Laboratories on November 27, 2017

During the mid of 19th century, in the Ganges Delta, a pandemic broke out in Jessore area of India, due to contaminated rice. This disease was quick to spread to the modern-day Myanmar and Sri Lanka. Fast forward to present times - we all know the disease as cholera ,as it was caused due to a bacterium named, Vibrio Cholerae¹.

By the year 1820, cholera had already spread in countries like Thailand, Indonesia and Philippines, killing 0.1 million people in Java alone². Thereafter, Cholera has been a regular cause of death among children worldwide. Though cholera is still a global threat, it majorly affects developing nations where proper sanitation and access to safe drinking water remain a distant dream³. India is also among those countries which are struggling to eliminate this disease to lower its mortality rates.

Every year at least 525,000 children under the age of 5 die due to diarrhea, out of a total 1.7 billion diagnosed cases across the globe.Lack of access to treatment is the root cause of these deaths. To deal with this situation, it is important that accessibility for proper vaccination is provided to sufferers of this disease, especially in underdeveloped countries, where the disease affects the most.

This concept of affordable and easy to access vaccine seems to have well understood by a rather new organization - Hilleman Laboratories, a joint venture partnership between Merck Sharp & Dohme (MSD) and Wellcome Trust.

Hilleman started with a mission to provide affordable vaccines to the world for life-threatening diseases. On 12th October 2017, Hilleman Laboratories announced the results of Phase I/II clinical trial of their novel Oral Cholera Vaccine Hillchol^TM, at the Vaccines for Enteric Diseases Conference 2017, held in Albufeira, Portugal.

The clinical study was conducted in partnership with icddr, b(International Centre for Diarrheal Disease Research, Bangladesh)

Dr. Ajit Pal Singh, Vice President, Clinical R&D, Hilleman Laboratories, summarized the results of the study, saying that, Hillchol^TM proved to be safe and tolerable when studied on the 840 subjects, including adults and adolescents. The Hikojima strain in the vaccine expresses both the Ogawa and Inaba serotypes. He said that the results of the study were encouraging enough for them to continue the development of the cholera vaccine.

The current situation where, demand for the vaccine exceeds its supply rate, this project by Hilleman will prove to be a boon in the cholera treatment.

Dr. Davinder Gill, CEO, Hilleman Laboratories, also reciprocated the same thoughts - "There is an urgent need for effective and affordable cholera vaccine for use in both the cholera outbreaks as well as mass vaccination campaigns, also recommended by WHO”.

The development of this affordable vaccine by Hilleman Laboratories will prove to be beneficial for the developing countries in their fight against cholera, causing millions of deaths every year.

This move by Hilleman Laboratories also aims at contributing in the initiative announced by WHO to reduce cholera by 90%, by the year 2030, as stated by Dr. Davinder Gill. WHO Global Task Force on Cholera Control (GTFCC)is offering an effective platform to all multi-sector technical partners, to help the countries in their fight against cholera.

GTFCC brings together government andnon-governmental organization which work together to develop training, materials and technical guidelinesfor cholera control.

1. http://www.who.int/mediacentre/factsheets/fs107/en/
2. http://www.history.com/topics/history-of-cholera
3. http://www.who.int/topics/cholera/about/en/

Read More

A war-torn Yemen is currently facing the world

By: Hilleman Laboratories on September 25, 2017

A war-torn Yemen is currently facing the “world’s worst cholera outbreak”, declared the United Nations recently. The ravaged country was on the brink of famine, and now it’s being destroyed by a humanitarian crisis of unprecedented proportions. According to International Health Authorities, the cholera outbreak has reached an estimated half a million people, while 5,000 more cases are reported each day. The disease has killed over 2,000 people since April 2017. 

Cholera, a water borne disease caused by the ingestion of infected food and water, is easily treatable with access to clean water, sanitation, replenishing fluids and good nutrition. But, the effects of a debilitating war that’s lasted for three years and counting has left long lasting depressions in Yemen. The public health systems have collapsed and is becoming difficult to achieve coverage. It is tragic, because the disease is vaccine preventable and contagious. A disease which can be cured today has taken the lives of so many.

“The total number of suspected cholera cases in Yemen this year hit the half a million mark in August  and nearly 2,000 people have died since the outbreak began to spread rapidly at the end of April,” WHO said in its statement.[2]

The ongoing war has devastated the country’s infrastructure and has left the majority of the population without access to basic services like clean water or even enough food. The levels of food insecurity and malnutrition are increasing, leaving the majority susceptible to a wide number of diseases. Medical attention is a scarce due to frequent bombings. The unlawful air-strikes have struck hospitals, food factories, prisons, trucks transporting food, schools and most recently a hotel. Each of these have shamefully targeted and killed civilians while displacing thousands.

“Yemen’s health workers are operating in impossible conditions. Thousands of people are sick, but there are not enough hospitals, not enough medicines, not enough clean water,” WHO Director-General Dr. Tedros Adhanom Ghebreyesus said in a statement. “To save lives in Yemen today we must support the health system, especially the health workers.” [3]

    

WHO and its partners are efforting to control the cholera outbreak while working closely with UNICEF, Yemen’s local health authorities to treat the affected and control further outbreak. They have sent thousands of bags of intravenous fluids to the country since April. The organization has also provided 525 beds with cleaning supplies and 112 kits for treating cholera. In partnership with UNICEF, WHO has established 2,924 diarrhea treatment beds as well as several oral dehydration therapy areas.

“We urge the Yemeni authorities – and all those in the region and elsewhere who can play a role – to find a political solution to this conflict that has already caused so much suffering. The people of Yemen cannot bear it much longer – they need peace to rebuild their lives and their country,“ Dr Tedros said.[5] 

According to World Health Organization, the right strategy and funding could eliminate the disease within a few years as the great news is that the world has access to safe, effective and affordable vaccines, a possibility which was unlikely before 2011. By vaccinating the population at risk and maintaining clean water, hygiene and sanitation, the disease would no longer pose a threat to global health. Such unforeseen epidemics like the Cholera outbreak in Haiti, Yemen, Bangladesh and India calls for innovative interventions to ensure quick accessibility of vaccines in limited-resource setting areas. One such example is the existence of heat-stable vaccines which holds the potential to ensure maximum coverage. The immunization gap could be bridged since they are not temperature sensitive driving down the logistics cost.

---

[1] https://www.usatoday.com/story/news/2017/06/28/yemen-facing-worst-cholera-outbreak-world-health-authorities-say/436858001/

[2] https://english.aawsat.com/n-al-rasheed/news-middle-east/yemens-health-minister-efforts-address-cholera-improving

[3] http://time.com/4900830/yemen-cholera-crisis-half-million

[4] http://www.who.int/emergencies/yemen/en/   

[5] http://www.independent.co.uk/news/world/middle-east/yemen-cholera-cases-half-million-civil-war-aid-healthcare-humanitarian-a7894141.html#gallery

Read More

Heat stable Rotavirus Vaccine: India Combats Diarrheal Deaths

By: Hilleman Laboratories on June 15, 2017

Rotavirus is a highly contagious virus, usually spread through contaminated water and food. The disease causes uncontrollable diarrhea leading to severe dehydration which can even cause death. It is the most common cause of diarrheal disease in young children throughout the world. According to the estimations of World Health Organization, nearly 215,000 children aged less than 5 years die globally from vaccine preventable rotavirus infections. The maximum number of children affected reside in low-income countries where children are malnourished and lack access to proper medical care. However, In India, it is the leading cause of moderate to severe diarrhea accounting for 40% of cases which require treatment. The vast majority of children in the country are affected by diarrhea than as compared to AIDS, malaria, and measles combined.



According to the Union Health Ministry, rotavirus diarrhea is responsible for about 78,000 deaths, 3.2 million outpatient visits and nearly 0.9 million hospitalizations every year. Therefore, in 2014, the rotavirus vaccine was included in the Universal Immunization Programme in 4 states, Himachal Pradesh, Andhra Pradesh, Haryana and Odisha and then in February 2017, the vaccine was included in Assam, Tripura, Rajasthan and Tamil Nadu. Even though the government is striving for maximum coverage where no child should die from vaccine-preventable diseases, it faces difficulties such as reaching remote areas, untrained health workforce, equipment, logistics and sub-optimal cold chain management.

The available vaccine for rotavirus vaccine loses its potency when exposed to temperatures outside the specified range which lie between 2° to 8° Celsius.As emphasized in a peer-reviewed medical journal, outdated vaccine supply, and distribution systems not only delay, but also limit the impact that vaccines have in safeguarding people’s health. Thus, understanding the global disease burden of rotavirus has on childhood mortality, Hilleman Laboratories leverages its research functions to establish a proof of concept for the development of an optimized oral heat-stable vaccine that will impact the health of millions of children in developing nations.

Hilleman Laboratories is improvising the existing oral rotavirus vaccine which will be thermostable i.e. the vaccine will be functional over a wider range of temperature thereby reducing the dependability on storage & refrigeration. This kind of Research & Development is needed to make effective vaccines that have a high efficacy percentage available in resource-limited countries so that they can be more easily used to decrease the impact of vaccine-preventable diseases. Hilleman Laboratories is using innovative technology for simple novel packaging, making it affordable and the vaccine will be lyophilized for easier administration. If the vaccine proves to be safe and immunogenic the vaccine could be brought to India, as early as 2020, aiding in bridging the gap in vaccine delivery says Dr. Davinder Gill, CEO, Hilleman Laboratories.

Read More

Three solutions setting the pace of Immunisation - Thermostability, Affordability and Availability

By: Hilleman Laboratories on May 22, 2017

The vaccine landscape is shifting, and new opportunities, challenges, and debates have pushed vaccines to the center of global health discussions. Thanks to vaccines and systematic immunization, the polio disease saw its final death knell. It is estimated that vaccines avert about 2-3 million deaths each year in all age groups and protect 83% (107 million) of infants worldwide from vaccine preventable diseases .

Immunity is gained without the consequence of being ill and without the risk of potential life-threatening complications from the disease. However, access to vaccines has been a critical issue in ensuring the health of children, especially in the developing countries. Access is currently limited due to limited money available for vaccine procurement, high prices of new vaccines for existing and emerging diseases and poor health delivery infrastructure in developing countries . Not just access, thermostability has been another cause for concern in case of vaccines. The World Health Organization (WHO) estimates that annually 10-50 percent of vaccines may be wasted globally because of temperature control, logistics and shipment-related issues. In low-resource settings, factors like tropical temperature, scarce resources, unreliable power, and long distances between healthcare facilities pose risks.

Innovation is the key to success!

As already discussed, a lot of factors contribute to vaccines not completely catering to those in need of it. The temperature sensitive nature of these vaccines leads to a loss in production as well as the supply chain. However, the last decade saw significant advances in developing, introducing and expanding the reach of vaccines globally. One of such measures was the ‘vaccine cold chain’ wherein vaccines are stored at refrigerated temperatures throughout the transport, storage, and handling of vaccines. The cold chain implies that the vaccine, from the time it is produced till the time it is consumed, stays in refrigerated conditions. Besides that, some companies are even researching methods to enhance the thermostability of vaccines. They have invented measures to maintain all the attributes of a vaccine even in unfavorable temperature conditions. Thermostable vaccines also help to decrease logistics cost by eliminating cold chain, which, in turn, allows for more economical pricing. As a result of this, vaccines can also be made available in remote and far-flung areas where temperatures are not naturally favorable.

Hence, it is fair to say that Thermostability, Affordability, and Availability go hand-in-hand and they hold the key to the success of immunization. The heart and soul of this field is innovation. Innovation is required to improve vaccine production as well as optimizing the supply chain. The recent wave of changes has created a tremendous opportunity for innovative technologies in this space, as companies that can help discover and deliver new vaccines could create enormous value.

Read More

The Low Cost Meningococcal ACYWX Conjugate Vaccine: A Boon For The Developing World

By: Hilleman Laboratories on May 15, 2017

Meningitis is the inflammation of the membranes that outline your brain and spinal cord. These membranes are called meninges, therefore, giving the illness, its name - “meningitis”. While viral meningitis is the most common, bacterial meningitis is more consequential. Lack of timely treatment can cause paralysis, stroke, seizures, sepsis, and even death. The symptoms of bacterial meningitis can begin quickly, sometimes as quick as in a couple of hours. In cases of development of the disease, one experiences nausea, vomiting, sensitivity to light, confusion and a rash of purple discoloration. There are several cases of bacterial meningitis –
1.) Streptococcus pneumoniae, also called pneumococcus
2.) Neisseria meningitidis, also called meningococcus
3.) Haemophilus influenzae type B, also called Hib
4.) Listeria monocytogenes
5.) Group B streptococcus
6.) E. coli

Amongst the leading causes of bacterial meningitis is “Neisseria meningitidis”; causes pneumonia, sepsis and other such infectious manifestations. The invasive disease affects 50,000 to 1.2 million people and is responsible for 135,000 deaths annually. As in the case of other infectious diseases, the majority of disease burden lies in developing countries. This includes meningococcal countries in the African meningitis belt, regions in South-East Asia as well as in the United States of America. Meningitis is also prevalent in Europe, the Eastern Mediterranean region and in Saudi Arabia. The recorded incidence of the endemic meningococcal disease is relatively low in India but such cases have occasionally appeared in the last 100 years. The disease is deadly and is contagious in people with close contact and can spread through coughing and sneezing. A person develops bacterial meningitis when bacteria gets into the bloodstream from the sinuses, ears or other parts of the upper respiratory tract.

There are 13 serogroups, but the majority of invasive meningococcal infections are caused by organisms from the A, B, C, X, Y, or W serogroups. While polyvalent conjugate vaccines targeting serogroups A, C, Y and W, are available, they are too expensive and therefore not widely used in developing countries due to affordability and accessibility issues. There are currently no low-cost polyvalent conjugate vaccines in the market that cover all five A, C, Y, W and X serogroups. Therefore, Hilleman Laboratories is currently working on a low - cost meningococcal ACYWX conjugate vaccine which provides protection against five types of serogroups. Researchers adopted a two- pronged strategy to develop low-cost combination vaccine for the treatment of invasive meningococcal disease.

“The role of the formulation in the vaccine scenario in terms of accessibility, affordability, and acceptability, besides the contribution in bridging the immunization gap in the country would also be assessed,” says Dr. Davinder Gill, CEO of Hilleman Laboratories. Developing Countries with high endemicity place an immense strain on the public healthcare system. The disease includes long-term risk of cognitive deficit, bilateral hearing loss, motor deficit, seizures, visual impairment, and loss of limbs due to tissue necrosis; the highest risks in low-income countries, where the burden of bacterial meningitis is greatest.

The novel cost Meningioccocal - ACYWX conjugate vaccine has the potential to significantly reduce costs and create new intellectual property allowing developing country manufacturers undertake more conjugate vaccine development projects. Technical success of the vaccines has been demonstrated in animal models. With accessibility and affordability issues in low-income countries, the vaccine could prove to be a boon for the developing nation.

Read More