Vaccines are currently the most effective barrier against contagious diseases and even certain types of cancer. There are immense needs to be covered. Many potential developments are underway, both in terms of preventive and curative treatments. New technologies could provide even further advances, particularly in terms of research, production and accessibility.
There is no disputing the fact that vaccination is one of the greatest successes of modern medicine. Many previously fatal illnesses have been curbed or even eradicated. Smallpox, which was the cause of 300 million deaths last century, was eliminated worldwide just 40 years ago. Polio, another fatal infectious disease, could soon follow suit. The illness is no longer in circulation in South East Asia, as the region was officially declared polio-free three years ago.
Several dozen vaccines have already immunised a significant proportion of the world’s population against dangerous infections including tetanus, diphtheria, whooping cough, measles, meningitis, pneumonia and influenza, or they have at least mitigated their impact. According to the World Health Organisation, vaccination saves between two and three million lives per year. In terms of requirements compared to costs, vaccines are one of the most profitable healthcare investments. All countries and age groups are concerned.
Although partly contested by public opinion, vaccines are the only viable defence against epidemic risks. Immunization coverage rates, which have been falling constantly for several years now, are a key factor in preventing the resurgence of certain diseases which were in decline, including mumps, German measles and measles, which have seen the number of cases increase dangerously over the past four years1. Any negligence in terms of vaccination should not be tolerated. The rule is a simple one: almost all of the target population must be vaccinated against a virus to prevent its resurgence in the medium to long term. The scientific community has set the critical coverage threshold at…95%.
Market taking off
Vaccines are like other medicines. Development takes time and is complex and costly, requiring cutting-edge knowhow, sophisticated equipment and heavy investments. Developing a new vaccine generally takes between 8 and 18 years and an average estimated investment of 800 million euros. For these reasons, there are four traditional key players in the industry, namely GSK, Merck&Co, Pfizer and Sanofi, representing two-thirds of current sales, at just over 27 billion euros. However, biotech companies have broken through into this strategic industry over the past few years, particular over the past few months. Although they are more agile, biotech groups lack the financial backing and technical expertise of the major pharmaceutical groups which are tending to set up partnerships with the most promising newcomers. The other notable factor is that Europe is the largest producer of vaccines (76%), far ahead of North America (13%) and Asia (8%). As an indicator of their supremacy, European companies invest two billion euros per year into R&D, which represents 71% of global investments2.
Driven by increasing demand and medical progress, the global market is expanding exponentially. According to the medical market intelligence group Alcimed3, the market could reach 80 billion euros in 2025, compared to 26 billion in 2011. Growth will be driven by vaccination programmes in developing countries, therapeutic vaccines and the generalisation of new administration methods. Future Covid-19 vaccines are not included in these projections and could therefore increase the estimate considerably.
From contagious diseases…
Despite regular progress, several contagious diseases are still not covered by a reliable vaccine. Malaria and HIV4, the two most deadly diseases are included in this category. After years of unavailability, the first antimalarial vaccine was approved 5 years ago. Although the vaccine has been widely used in the countries most affected on the African continent, it has had limited success. The HIV vaccine on the other hand has sparked strong hopes. A team from the San Diego5 Scripps Research unit has recently finalised the development of an experimental vaccine capable of producing antibodies which neutralise several strains of the virus. After successful testing in rabbits, this ambitious treatment will soon be tested on humans.
As with the new coronavirus, (re)emerging viral infections represent the greatest challenge in vaccine research. Ebola is undoubtedly one of the most virulent viruses, with an average fatality rate of around 50% and up to 90% in certain endemic regions. An initial preventive vaccine was approved for use last November and is now recommended among adults aged 18 and over. Although there are still doubts over its immunity duration, the vaccine has a clinical efficiency rate of between 65 and 100%. Although this is a high level, it is still insufficient as it targets only one single strain known as the Zaïre Ebola virus, as was also the case with the second type of vaccine approved this summer covering adults and children aged one year and older. A lasting solution may soon be developed. America researchers6 have recently presented preclinical results for a new combined universal vaccine which is efficient against the four different strains of the disease affecting humans.
… to chronic illnesses
A large number of prospective preventive and curative vaccines are under development, particularly in oncology. Several prophylactic vaccines can already partially or fully prevent liver and uterine cancers. Although they do not directly cure some pathologies, they contribute towards protecting populations against their more critical forms by arming individuals against the potentially fatal consequences of diseases like hepatitis B and human papillomavirus (HPV 16 and 18 are the cause of 70% of cervical cancers and precancerous lesions). Even more surprisingly, vaccination may be indirectly associated with curing some types of cancer in their metastatic stage, including lung cancer. A French research team7 claims to have identified a procedure which can reduce resistance to immunotherapies, using a vaccine usually recommended to prevent gastro-enteritis. Capable of killing in vitro cancerous cells, its association with standard immunotherapy also triggers a powerful in vivo anti-tumour immune response, although inefficient when used alone. The new approach has been tested on animals and could help a large number of patients, as immunotherapy functions in only 10 - 25% of cases.
Specific research domains are applied to chronic illnesses on a much larger scale. Another French research team is developing a vaccine which modifies the composition and functions of intestinal microbiota8. The vaccine, which has been tested on mice, appears to have a protective effect against chronic inflammation such as Crohn’s disease, diabetes and obesity. The researchers claim that the strategy deployed could be used in humans.
Technological promise
The technological revolution, acting like a particle accelerator, will amplify the transformation currently underway. A whole new generation of vaccines, in addition to Covid-19, have almost reached their production stage. Experts believe that mRNA technology can be used in numerous potential applications against several diseases, including cancers. These types of products could potentially be developed more rapidly and more cheaply and above all, more efficiently and could also be safer to use. Other breakthroughs in terms of digital progress will also have a significant impact on vaccine manufacturing processes. Structural changes will contribute to reducing production costs and improving productivity. Around the world, the major industrial groups in the pharmaceutical sector are investing massively to build flexible digitalised sites in response to the requirements of industry 4.0.
Certain innovative procedures may also speed up rollout among populations. An international partnership between the GAVI vaccine alliance and the London-based start-up Simprints has been set up to strengthen infantile vaccination monitoring in developing counties, using fingerprinting techniques to facilitate identification. Data is collated in rapidly accessible electronic medical dossiers. Under initial tests carried out in Bangladesh, Zambia, Nepal and Benin, the biometric identification technology developed by Simprints, which is a non-profit organisation, appears to have demonstrated optimal efficiency (99%). According to GAVI, some 20 million children are currently deprived of vaccines due to a lack of official identification.
Vaccination is a constant global issue representing one of the principal sources of progress in terms of healthcare and sustainable development. Due to their highly dynamic innovation, vaccines also represent one of the most promising sources of hope in modern medicine. Candriam, as an experienced observer, plans to back the most promising schemes which will be of the greatest use to the community, drawing on a network of experts to identify, support and value the companies producing tomorrow’s solutions.
Covid-19: a test case
Covid-19 succinctly resumes all of the major vaccination challenges… as well as representing an absolute healthcare emergency. For the past 10 months, researchers have been mobilised around the world to develop an efficient treatment, including the use of unprecedented methods in order to gain time.
Less than a year after the appearance of the first cases in China, thirty or so candidate vaccines are currently at an advanced stage of development. Excluding the Chinese and Russian vaccines, for which clinical data has not yet been validated by the international scientific community, the best chances of success are in the US, where two laboratories – Moderna and Pfizer* – filed for FDA approval at the end of November. It remains to be seen how long the health authorities will take to analyse the data and whether they will grant authorisation. Mass production and distribution will then follow. Once the precious vaccine is available, certain categories of the population including key workers and vulnerable individuals will probably be vaccinated first, such as old people, the chronically ill, healthcare professionals and public sector vital service staff. Given the current high level of uncertainty, the rollout date is impossible to estimate.
One thing is sure however, public acceptance will be a fundamental factor in stemming the pandemic. The World Health organisation, which is fully engaged in debunking fake news, will be able to count on the support of certain highly popular social media platforms. Two initiatives worth highlighting are the schemes launched by Facebook, which has now banned advertising discouraging vaccination from all of its media sites, while YouTube systematically deletes videos relaying false information concerning the future vaccine.
* The Pfizer vaccine has been developed jointly with the German company BioNTech.
Towards new therapeutic approaches
Medical progress has opened up a multitude of possibilities. Over the past few years, new techniques have facilitated the development of more efficient products which are also safer. Among these techniques, genetic engineering, combining vectors, inverse vaccination and chimeric vaccines provide higher chances of success. Inverse and chimeric procedures have been successfully used to develop vaccines against Dengue fever and invasive meningococcus B infections.
Adjuvants, which enhance or guide immune responses as a function of the target micro-organisms, are unfamiliar and arouse suspicion. Originally based on aluminium, the arrival of lipid-based adjuvants has now opened up a fresh perspective. For example, this type of adjuvant was recently used in the composition of vaccines against papillomavirus and shingles infections.
Further significant progress is also expected to vary administration methods, via trans-dermic patches or through oral, nasal, sublingual, rectal or virginal mucous membranes. Already used on a relatively small scale, these new methods stimulate the immune response and improve patient comfort.
Vaccination optimisation represents another major challenge which will inevitably involve the deployment of new increasingly personalised strategies. Besides pregnant women, the elderly and immunocompromised and high infection risk patients will be the target groups. Several breakthrough innovations may also make a contribution, including a new anti-flu vaccine with a viral dose four times higher than current versions, at 60 micrograms vs 15. Currently available in North America, this new vaccine has been administered to some over 65s.
[1] Measles cases increased by 476% from 2016 to 2019 (source: WHO).
[2] Source : Vaccine Europe
[3] The changing global vaccine market: innovative therapeutic vaccine technologies Alcimed (March 2016).
[4] Tuberculosis caused 1.2 million deaths last year; 770,000 people also died from HIV related illnesses (source: WHO).
[5] Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability, Scripps Research (November 2019).
[6] A Bivalent, Spherical Virus-Like Particle Vaccine Enhances Breadth of Immune Responses against Pathogenic Ebola Viruses in Rhesus Macaques, Cincinnati Children's Hospital Medical Center (April 2020).
[7] Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade, Centre de Research de Cancérologie de Lyon / Centre Léon Bérard / Gustave Roussy (October 2019).
[8] Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases, Institut Cochin (December 2019).