Vaccination is the most reliable way to reduce the likelihood of a pandemic or epidemic, reducing the outbreak of infectious diseases. Thanks to the rapid advancement in medical sciences and increasing adoption of technologies, vaccines are becoming more effective and providing positive outcomes. Never in our lifetimes has there been a greater emphasis on public health or a greater understanding of how information may influence patterns of health and well-being at all levels, from the personal to the societal. The COVID-19 pandemic accelerated the global adoption of digital health despite obstacles and risk aversion. The epidemic highlighted the need for innovative care models and faster information flow, which has resulted in a rapid rise in the use of digital health, particularly virtual care, in many nations.

Digital Vaccines

Enhanced focus on virtual healthcare leveraging advanced technologies has led to the rapid development of digital vaccines. A subcategory of digital therapeutics, digital vaccines aim to provide virtual care to patients via smartphones, tablets, and other devices. The rising incidence of chronic and neurological disorders has allowed the widespread scaling of frequent and personalized interventions at a low cost, which has fueled the growth of digital vaccines around the world.

The burden of chronic disorders is increasing at a rapid pace as patients struggle adhering to prescribed medications and implementing behavioral changes needed to stabilize the conditions. These challenges are creating a need for comprehensive disease management enabled by digital technologies. Hence, digital therapeutics have been gaining a lot of traction for personalized coaching, real-time customized health recommendations, medication adherence, etc. There is a growing body of evidence through various clinical studies that indicate that digital interventions work and improve patient outcome. Digital vaccines deliver evidence-based therapeutic interventions to improve the management of chronic diseases and provide patients with more treatment options. These vaccines present a promising solution for many chronic diseases such as Alzheimer's, type 2 diabetes, congestive heart failure, and cancer, among others.

New Advances in Digital Vaccines Market

Many players attempt to disrupt the disease management industry and create fresh, cutting-edge approaches to manage chronic illnesses. New-age start-ups provide more radical and unrestricted perspectives while incumbents offer a far more in-depth understanding of the issues. In the end, both start-ups and established players are essential for disrupting the market and scaling up solutions for wider audiences.

A bio and health tech startup, FriendsLearn has developed digital vaccines to non-invasively induce a neural response and immune response for lowering the risk of communicable and non-communicable diseases among kids. These digital tools have shown promising results for stimulating the brain-gut-immune system at the cellular biomarker level to reduce the risk of diseases like diabetes, cardiovascular disease, hypertension, cancer, ADHD, dementia, and COVID-19. The startup has harnessed machine learning-deep learning, neurocognitive computing, neural networks, gamification, AR/VR, and mobile app technology to build the digital vaccine. The gamified content delivered by mobile app called Fooya! has an appropriate compilation of neurocognitive training mechanisms. When the child uses sensory pathways like sight, touch, and hearing, a certain pattern of neural response is created in the brain, leading to transference. The gamified content trains the kid to make healthier choices that could help them make informed choices in terms of foods & beverages, which lead to lifestyle disorders such as obesity, diabetes, etc.

To provide patients with neurological injuries and conditions like stroke, traumatic brain injury, sclerosis, Parkinson's disease, etc. with engaging and immersive therapies in the convenience of their own homes, the digital neurology startup Mindmaze has developed a gamified digital neurotherapeutics. The FDA-cleared MindMotion platform help patients regain the functionality of their arms through movement-tracking games. As the burden of neurological disorders continues to rise, developing such technologies could help in better prevention and treatment strategies.

In May 2021, Northwell Health and Pear Therapeutics partnered to offer patients with opioid and substance use disorders digital therapeutics. FDA-approved Prescription digital therapeutics (PDTs) allow patients to have 24/7 access to evidence-based tools such as reSET and reSET-O to supplement their therapists' in-person or remote addiction therapy. The randomized controlled trials found that the real-world therapeutic engagement with reSET-O leads to better abstinence and retention in the treatment. Besides, both the products provide patients algorithm-driven cognitive behavioral therapy, fluency training, and contingency management as a complement to outpatient counselling. Therapists can simultaneously use this information to prepare for in-person and remote consultations.

The National Center for Telehealth and Technology of the US Department of Defense has launched a computer-based virtual world for military soldiers to deal with post traumatic stress disorder (PTSD). The participants can create a virtual avatar to play through scenarios that seem realistic to combat their mental health issues. The users are led through a role-playing scenario that resembles a crowded marketplace similar to that in Iraq or Afghanistan. During the scenario, the users monitor their reaction and stress levels and then they are sent via virtual flight home where they encounter everyday activities like shopping and face large crowds. Through the program, the users can navigate through different situations when they might not actually be comfortable in real life. The interactive simulations and experiences can really help the military personnel to learn about the causes and symptoms of PTSD.

According to TechSci Research report on “Digital Vaccine Market- Global Industry Size, Share, Trends, Opportunity, and Forecast, 2018-2028F, Segmented By Device Type (Smartphone, Tablets, Others), Application (Diabetes, Infectious Diseases, Cardiovascular Diseases, Others)”, the global digital vaccines is expected to grow at a formidable rate during the forecast period. The market growth can be attributed to the rapid emergence of cutting-edge technologies such as Internet of Things, virtual reality, smartphone apps, and artificial intelligence. Besides, rising need for needle-free vaccines in treating patients for various diseases and phobias and rising VC investment in digital vaccine startups are contributing to the market growth.

Digital Vaccine Market Drivers

• Rise of Non-Communicable Disorders

Every year, 41 million people lose their lives to non-communicable diseases, according to World Health Organization statistics. Growing incidences of non-communicable diseases across all age groups and geographical areas are putting a lot of burden on healthcare facilities and leading to rising healthcare costs. Besides, lack of awareness and limited accessibility and affordability to the right treatment are contributing to rising mortality rates across the world. Prevalence of many lifestyle disorders such as diabetes, cardiovascular diseases, hypertension, etc. can be managed by making behavioral and lifestyle changes. Hence, rising lifestyle disorders and enhanced awareness among people for health can result in the greater adoption of digital vaccines by individuals and medical facilities alike.

• Enhanced Focus on Personalized Medicines

Since most diseases today are classified on the basis of affected organ, the diagnosis reveals little about the nature of a particular patient’s illness. Personalized medicine or precision medicine require genetic, genomic, DNA, or molecular testing that helps to make a more accurate diagnosis and improve treatment. These biomarkers provide detailed cellular information driving a patient’s disease and enable healthcare practitioners to suggest beneficial therapies that lead to better outcomes. Digital vaccines provide customized treatments to patients based on their individual needs. Hence, rapid adoption of personalized medicines could fuel the growth of digital vaccines market.

• Increase in Clinical Trials and Patents of Digital Vaccines

High investments for the research and development of digital vaccines have led to an increased number of clinical studies, most of which has demonstrated positive outcomes. Between 2020 and 2022, the VC investment in European Digital Therapeutics has grown to USD645 million, which reflects almost 9 times growth compared to 2016. As biopharma companies are realizing the untapped potential of digital vaccines, they are ready to invest in more clinical trial studies for further expansion.

Neoantigen Cancer Vaccines

Cancer is one of the leading causes of death around the world, accounting for nearly 10 million deaths in 2020, as per WHO statistics. Cancer is a serious threat to human health since it is usually difficult to treat even if it is discovered. Different patients react to different treatments in different ways, which has led to the growing need for developing personalized cancer treatments. The development and regulatory approval of tumor immunotherapies, such as cancer vaccines, adoptive cell therapy, and antibody-based therapeutics, especially for solid tumors, have been accelerated by recent developments in neoantigen research. Neoantigens cause an immune response that is not controlled by central and peripheral tolerance because they are recognized as non-self. The rapid advancement of next-generation sequencing and bioinformatic technology has allowed for the rapid identification and prediction of tumor-specific neoantigens and development of neoantigen cancer vaccines.

Neoantigen-targeted cancer vaccines work by stimulating or enhancing an immune response to the neoantigens found in a particular patient. Even though a cancer patient may already be naturally immune to some of these neoantigens, a vaccine can greatly enhance that immune response. The vaccine may occasionally induce defense against neoantigens. Then, the neoantigens present in the vaccine activate T-cells. Activated T-cells multiply, form any immune army to kill any cells that contain neoantigens that lead to cancer. Neoantigen vaccines consisting of lab-made versions of neoantigens along with adjuvant provide “danger signals” and alert the immune system of the threat. Personalized neoantigen vaccines utilize RNA, or DNA that contains the code of neoantigens, which instruct the cells in the body to translate the RNA or DNA code and make neoantigens, which further stimulates immune response. Clinical trials conducted with patients demonstrated that neoantigen-directed vaccines are safe and feasible.

However, recent work by international consortia has shown that by incorporating important regulating characteristics of immunogenicity, in silico predictions of immunogenic neoantigens can be significantly improved. Additionally, by consistently including additional mutation types found in the exome, such as deletions, translocations, and inversions, the neoantigen discovery space, which is currently largely limited to single nucleotide variants, can be significantly expanded. Epigenetics and ribosome profiling, two cutting-edge methods, may expand the discovery area beyond the exome. Biopsies from numerous tumors or tumor locations, serial tumor biopsies, or circulating cell-free tumor can all be used as methods to combat tumor heterogeneity by obtaining a potentially more comprehensive spectrum of tumor variants.

Likang Life Sciences has received approval by China’s Center for Drug Evaluation for the clinical trial of its personalized neoantigen-targeted vaccine. The Likang mRNA editing technology can encode multiple antigens at once while maintaining rapid and efficient expression, which makes it ideal for the development of personalized cancer treatments. The company claims that the combination of an mRNA vaccination and a DC vaccine represents a potential advancement in the field of personalized neoantigen treatment and offers patients a reliable and secure method of battling cancer.

Growing Collaborations for Neoantigen Vaccine Development

Global pharmaceutical companies, Moderna and Merck, have created a unique mRNA personalized cancer vaccine (PCV), mRNA4157, which combines proven and identified neoantigens, projected neoepitopes, and driver gene mutations into a single mRNA concatemer. In two clinical trials, the vaccine is being assessed as a monotherapy and combination therapy. The preliminary results of the clinical trial show that the vaccine, whether administered alone or in combination, was well tolerated by participants at all dosages examined and produced desired T cell responses, which were specific to neoantigens. Patients in the third stage of ongoing trial showed positive results with the personalized cancer vaccine, reducing the risk of cancer returning by 44% compared to the standard approach of removing the melanoma via surgery.

The United Kingdom government has announced to partner with one of the largest mRNA companies, BioNTech to trial personalized cancer vaccines and other diseases. The initiative aims to advance the mRNA vaccination technology that BioNTech gained notoriety for creating, and which proved to be effective at preventing COVID-related significant illness and death. By 2030, the government aims to provide 10,000 patients in UK with personalized therapies whose clinical trials are expected to start in the coming months.

In 2022, PhysIQ and CellCarta collaborated to potentially transform vaccine development through a more individualized and precise approach. As per the agreement, the company will launch the VIII (Vaccine-Induced Inflammation Investigation) study, which will focus on early, unique human reactions to vaccinations as pharmaceutical companies issue vaccines at a faster rate. Throughout this, medical-grade biosensors will be used to remotely monitor the physiology and immune system activation at all times. By spotting tiny changes just hours after vaccination, the cutting-edge artificial intelligence-based digital platform and immunologic biomarkers will make it possible to construct personalized baselines.

According to TechSci Research report on “Global Neoantigen Cancer Vaccine Market By Product (Personalized Neoantigen Vaccine, Off-the Shelf Neoantigen Vaccine), By Neoantigen Type (Synthetic Long Peptide (SLP), Nucleic Acid, Dendritic Cell, Tumor Cell), By Route of Administration (Intravenous, Intramuscular, Transdermal, Others), By Cell (Autologous, Allogenic), By Technology (RNA Sequencing, Whole Genome Sequencing, HLA Typing), By Delivery Mechanism (Liposomes, Virosomes, Electroporation, Gene gun, Others), By Application (Lung, Melanoma, Gastrointestinal, Brain Cancer, Others), By Region, Competition, Forecast & Opportunities, 2026”, the global neoantigen cancer vaccine is projected to grow at a significant rate. The growth can be attributed to factors such as rapid innovations in technology as well as infrastructural development. Besides, rising investments by governing bodies and healthcare providers is expected to boost the growth of global neoantigen vaccine market.

How can MAPS Technology Lead to The Development of Safer and Effective Vaccines?

Researchers are experimenting with novel approaches to infectious disease prevention and searching for effective vaccinations against bacteria and viruses. Their goals include incorporating more pathogen strains—disease-causing organisms—and diverse diseases into a single vaccination in order to boost immune responses and offer longer-lasting protection. A new era in the field of vaccine research began with the introduction of Multiple Antigen Presenting System, or MAPS technology, which was employed to produce vaccinations in record time during the pandemic. Compared to traditional conjugation technologies, the novel technology offers higher valency, offering greater protection against common pneumococcal serotypes and possibly producing better immunogenicity than current vaccines.

The aim of MAPS technology is to provide broader protection by mixing various sugar and protein antigens from the bacterial surface in one vaccine, which the immune system recognizes and then activate various immune system components. The protein antigens can trigger an extra T-cell and antibody response, whereas the sugar antigens, known as polysaccharides, have the ability to generate an antibody response. Additionally, MAPS technology facilitates and speeds up the production of novel vaccinations. As infections are becoming hard or sometimes impossible to treat due to drug resistance from antibiotics medications, MAPS technology could become an important tool to counter bacterial pathogens that often spread in healthcare facilities and pose risks for healthcare providers.

GSK is set to acquire a clinical-stage biopharmaceutical company, Affinivax for USD3.3 billion for gaining access to the MAPS technology for the development of a novel class of vaccines, the most advanced of which are next-gen pneumococcal vaccines. Despite the availability of pneumococcal vaccines, there is still a considerable unmet demand for the treatment of pneumococcal diseases such as pneumonia, meningitis, bloodstream infections, and less severe illnesses like sinusitis and otitis media. The primary reason for this is that there are several pneumococcal serotypes, but only a small number of them are included in the current vaccines because of the level of immunological interference seen when employing the available conjugation technology.

Expanding Use of mRNA Technology for Vaccines

Vaccines aid in the prevention of infection by training the body to combat foreign invaders such as bacteria, viruses, or other pathogens. Each vaccine stimulates an immune response by introducing a small amount of a specific bacterium or virus into the body. Majority of vaccines contain dead or weakened germs or viruses. Instead of using a piece of a real bacteria or virus, scientists have created a new kind of vaccine that uses a molecule known as messenger RNA (mRNA). A particular kind of RNA called messenger RNA is required for the synthesis of proteins. When cells are done producing a protein, they swiftly degrade the mRNA. Vaccine-derived mRNA does not enter the nucleus and does not change DNA. Although the mRNA technology has been around since the 1970s, the first mRNA-based COVID-19 vaccine was authorised for emergency use in late 2020. Due to the success of mRNA technology, researchers are looking for ways the mRNA technology could be advanced and its significance for accelerating vaccine development. People who receive an mRNA vaccination are not exposed to the virus and cannot contract the infection through the vaccine.

Lipid nanoparticle (LNP) technology, a more recent development in the usage of mRNA, is a major and recent improvement in the synthesis of mRNA vaccines. By encasing the mRNA in lipids, LNPs make it easier for mRNA to be delivered to cells, and the method can transport mRNA to specific cells. Production of mRNA vaccines can be completed more quickly than with conventional vaccines because this approach does not need viral components. Another benefit of mRNA technology is that it can be utilized to create vaccines for viruses that might be difficult to identify or culture in the laboratory.

How does mRNA Vaccines Work?

Messenger RNA contains the instructions that directs the cells to make protein using its natural machinery. As a part of vaccine's delivery mechanism, mRNA travels within a protective bubble called Lipid nanoparticle to enter cells smoothly. Once inside, the cells start reading mRNA as a set of instructions for building proteins to match up with the parts of the pathogen. Then, the immune system recognises that the protein is foreign as part of a typical immunological response and creates specialised proteins known as antibodies. By identifying specific viruses or other pathogens, adhering to them, and designating the pathogens for eradication, antibodies aid in the body's defence against infection. Therefore, when the true virus appears, the body may be able to identify it and raise the alert to help the body fight off infection and disease.

Pfizer and BioNTech have collaborated for the Phase ½ trial for exploring the safety, tolerability, and immunogenicity of the mRNA vaccines against shingles (also known as herpes zoster, or HZ). Shingles are caused by varicella-zoster virus (VZV), and it affects millions of people around the world every year. Although there are already shingles vaccines that have been licensed, Pfizer and BioNTech hope to use mRNA technology to create a vaccine that has high efficacy, is well-tolerated, and is cost-effective to produce internationally. The firms' COVID-19 vaccine will make use of the unique antigen technology from Pfizer and the patent mRNA platform technology from BioNTech. The many forms of the glycoprotein E (gE) on the surface of the varicella zoster virus are encoded by the mRNA shingles vaccine candidates. After the virus is reactivated in nerve cells, the gE protein is crucial for viral replication and cell-to-cell spread.

The new breakthrough has established itself as a promising alternative to the conventional vaccine methods since it is safe for immunocompromised patients, quick to manufacture, and cost-effective. The opportunities made possible by the COVID-19 mRNA vaccine's success in the current biotech landscape are very exciting. The development of mRNA therapies that could treat or prevent a variety of other damaging diseases and ailments, such as influenza, HIV, Lyme disease, Ebola, Zika virus, and even cancer, is now under progress in clinical research studies. Additionally, clinical researchers are investigating the potential function of mRNA in the synthesis of proteins that are absent in conditions such cystic fibrosis, diabetes, and sickle cell anaemia. An exciting development in medicine, the new era of vaccination has the potential to have a significant impact on how doctors protect and treat their patients.

According to TechSci Research report on “mRNA Vaccine Market - Global Industry Size, Share, Trends, Opportunity, and Forecast, 2018-2028, Segmented By mRNA Type (Nucleoside-modified mRNA, Unmodified mRNA, Self-Amplifying mRNA), By Application (COVID-19 mRNA Vaccines, Non COVID-19 mRNA Vaccines, Others), Region and Competition”, the global mRNA vaccine market is expected to grow at a formidable rate during the forecast period. The market growth can be attributed to the rising incidences of cancer, genetic abnormalities, and viral infections.

How are mRNA Vaccines Different from DNA Vaccines?

Both DNA and mRNA vaccines use genetic materials that code for the pathogen's spike protein to elicit an immune response whereas conventional immunizations do so by using a pathogen (virus or bacteria) that has been weakened, injured, or rendered inactive. DNA vaccinations use small DNA molecules (plasmids) whereas mRNA vaccines use messenger RNA from the pathogens. Despite their similarities, DNA and mRNA vaccines differ significantly in a number of important ways. They differ in terms of mode of action and administration, as well as in terms of storage and transportation requirements, aside from the genetic material needed to create the actual vaccines.

DNA vaccines, such as recently developed ZyCoV-D vaccine in India, utilizes plasmids carrying the gene coding for the SARS-CoV-2 spike protein. Once the plasmid enters the nucleus of the human cell, the genetic material is converted into mRNA, which then travels to the cytoplasm where it is converted into viral or bacterial protein. Since the immune system does not recognize the protein, it raises a response to stimulate the antibody production and fight foreign material. So, while DNA vaccines need to enter the nucleus and then go all the way back to cytoplasm, mRNA require a much shorter route comparatively. As a result, mRNA vaccines generate higher immune response, which may provide a high level of protection against pathogens, but their resulting side-effects may limit their applicability.

In addition, while mRNA vaccinations are supplied intravenously, DNA vaccines transmit the genetic code of the pathogen into the cell by a brief electrical pulse utilizing a specialized instrument. Compared to mRNA vaccinations, DNA vaccines are substantially more temperature stable. Plasmid DNA vaccines are more stable and simpler to store and carry than mRNA vaccines, which have strict storage and transportation requirements and are therefore, much more difficult to distribute, especially in developing countries.

Researchers are looking for methods to improve delivery methods for DNA vaccines and induce a more potent response from immune system. Leveraging injection-free system for delivery of vaccine, Immunomic Therapeutics would start phase 1 clinical study of their plasmid DNA vaccine ITI-3000 in skin cancer patients.

The COVID-19 DNA vaccine, ZyCoV-D, developed by Zydus Cadilla is the first DNA vaccine to be approved for use in humans. ZyCoV-D involves the use of needle-free device that uses high pressure to help vaccine penetrate the skin surface. a number of human trials. Additionally, scientists are researching DNA vaccines against many cancers, such as pancreatic, breast, and cervical cancer. DNA vaccines can instruct the immune system to identify and eradicate tumor cells by teaching it how to recognize and express various proteins from healthy cells. Moreover, scientists are also evaluating the potential of DNA vaccines against various infectious diseases caused by HIV, Ebola virus, Zika virus, influenza, herpes virus, and human papillomavirus.

According to TechSci Research report on “Human DNA Vaccine Market - Global Industry Size, Share, Trends, Competition, Opportunity, and Forecast, 2018-2028 Segmented By Mode of Administration (Intramuscular, Subcutaneous, Intradermal, Others), By Application (Oncology, Tuberculosis, HIV, Human Papillomavirus, Others), By End User (Hospitals & Clinics, Biotechnology & Pharmaceutical Companies, Academic & Research Institutions, Others), By Region and Competition”, the global human DNA vaccine is anticipated to grow at a significant rate. The market growth can be attributed to the increase in number of antibiotics resistant pathogens and growing prevalence of different diseases are contributing to the growth of the global human DNA vaccine market.

Nanoscale Technology to Boost Vaccine Development

Danish researchers have developed a new tool using DNA nanotechnology for synthesizing and screening molecules that could speed up development of vaccines and other pharmaceutical products. The process, known as "single particle combinatorial lipidic nanocontainer fusion based on DNA-mediated fusion" or SPARCLD method, employs minute soap-like "bubbles" to synthesize more than 40,000 distinct molecules on a pinhead-sized surface. By employing DNA nanotechnology, the bubbles create "nano-containers" inside of which molecules can be created. On a square millimeter, 42,000 nanocontainers can fit. The technology, integrating aspects of nanotechnology, chemistry, and machine learning, has the potential to allow extremely rapid and efficient screening of thousands of candidate molecules for the production of pharmaceuticals and vaccines. Besides, SPARCLD can save a lot of time, effort, material, manpower and energy.

When referred to as liposomes, some of the "bubbles" are attached to a surface while others are free to float. A specialized microscope may be used to detect fluorescent markers and a unique DNA sequence found in each bubble. Multiple combinations of DNA fragments can be formed and observed in real time using the microscope as the bubbles float and randomly fuse. The microscope pictures are decoded by a machine learning algorithm, which then classifies the various 'fusion sequences' that result from this procedure.

Nanovaccines: An Emerging Strategy for Cancer

Numerous strategies based on immune system modification have been developed to treat cancer, and several of these techniques have shown promise in clinical trials. One of these cutting-edge approaches to treating cancer that has long been considered is the use of cancer vaccines. The goal of this type of vaccine is to induce potent anti-tumor immune responses, the targeted destruction of tumor cells with little harm to healthy cells, and the development of immunological memory against tumor antigens. Creating vaccines with delivery systems like nanoparticles (NPs) can improve both antigen presentation by APCs to effector lymphocytes and antigen delivery to antigen-presenting cells (APCs). Nanovaccines are primarily used to treat cancer by triggering anti-tumor immune responses and blocking immunosuppressive ones in the tumor microenvironment. By encasing antigens in nanocarriers, these vaccines boost antigen stability and stop their deterioration. Additionally, using adjuvants in addition to antigens helps speed up the co-delivery and capture process by APCs, enhancing the vaccine's immunogenicity and durability.

The utilization of NP-based delivery vehicles such as virosomes, liposomes, micelles, microemulsions, dendrimers, and nanogels could offer a potential solution to overcome limitations of conventional vaccination adjuvants. According to research studies, nanovaccines can improve the delivery of antigens and adjuvants, antigen presentation by APCs, promotion of innate immune responses, and powerful effector T cell responses to kill harmful microbes and tumor cells with little to no toxicity or negative effects. Thus, the development of potent immunotherapeutic formulations for human malignancies can greatly benefit from the use of nanovaccines.