WHY ORAL VACCINES?
Quick answers to frequently asked questions
WHY
The international spread of infectious diseases, such as Covid-19, constitutes a global health security problem. The best strategy to prevent them is vaccination, which is one of the most cost-effective health interventions. Thanks to vaccination, many diseases have been controlled and, in some cases, eradicated. However, fear of the injection, due to pain, is one of the many factors that lead people to delay or refuse vaccinations and decrease vaccination rates.
HOW
The new patent filed by VacciMed-oral GmbH is based on the use of Variable Surface Proteins or VSPs of the Giardia lamblia parasite, which contain unique properties as an original strategy for the generation of oral vaccines due to their outstanding resistance to proteases and pH changes, characteristic of the gastrointestinal tract, and to their high immunogenicity. This innovative development allows combining the adjuvant and protective properties of VSPs with antigens of other disease-causing agents to generate new and efficient vaccines for oral administration to reduce morbidity and mortality due to infectious diseases, including SARS-COV-2, which stalks mankind.
Finally, when vaccines are administered orally, they are exposed to the mucosal immune system, which generates a systemic response, as well as a response in mucous membranes (gastrointestinal tract, respiratory tract, etc.) which are the main site of entry of SARS-COV-2, among others, conferring a more complete protection. In addition, a valuable fact to highlight is that VLPs are classified as subunit vaccines since they do not contain the entire microorganism, but lack the genetic material of the virus and are therefore safer than attenuated or inactivated vaccines, allowing their application to immuno-compromised persons (newborns, pregnant or immuno-deficient persons).
Examples of such vaccines are those reported against Influenza Virus (Flu) (Nature Communications, 2019) and SARS-CoV-2 (Covid-19) (Frontiers in Immunology, 2022), which have demonstrated excellent results in animal models regarding not only protection against subsequent infections but also inhibition of transmission of such viruses among susceptible hosts, all due to the generation of a strong mucosal immunity.
The advantages of oral administration of other common (since long-time approved) vaccines are obvious: There is no fear of needles and syringes, and there is no need to inject the vaccine, thus increasing the acceptance of vaccination in the population. Disposable syringes are not required, and the cold chain is usually not necessary – both of which are considerable cost advantages – all factors that would be particularly important for developing countries. We assume that once the process for converting a commonly used vaccine that has so far been injected into an oral vaccine has been approved, the following process for other already approved vaccines will be significantly simplified.
The versatile oral vaccine platform could also come into use in the veterinary field, e.g., to give vaccine protection against viral diseases in fish and poultry farms. The vaccine, in these cases, can be mixed into the feed. First trials with this method were promising in chicken farming (vaccine protection against avian influenza). Other applications in the veterinary field are highly required.
The developed and patented strategy has been shown to generate long-lasting systemic and mucosal protective responses. The oral route of administration provides many benefits over traditional injectable vaccination:
| Criteria | Oral Vaccines | Injectable Vaccines |
| Administration | One of the primary benefits of oral vaccines is that they offer a painless and non-invasive mode of administration, eliminating the discomfort associated with injections. Oral vaccines are easier to administer and do not require trained healthcare professionals, which can be beneficial for mass immunization.[1] | Injectable vaccines require the use of syringes and trained healthcare professionals for administration, which can be a limitation for mass immunization. This necessity poses challenges in regions where there is a shortage of skilled healthcare workers.[2] |
| Accessibility | There are a limited number of mucosal adjuvants available for oral immunization, which can affect immune activity.[8] | Injectable vaccines typically necessitate a cold chain for storage and transportation to maintain their efficacy. This requirement poses logistical challenges, especially in regions with limited infrastructure or geographical isolation, where maintaining a continuous cold chain is difficult. Injectable vaccines face hurdles in regions affected by war, conflict, or geographical isolation, where the transportation of medical supplies and the deployment of trained personnel can be impeded. |
| Cross- Infection | Since oral vaccines eliminate the need for needles, there is a lower risk of cross-infection due to contaminated needles. This contributes to a safer vaccination process for both patients and healthcare providers. | There are needle-associated risks involved in the administration of injectable vaccines, which can be a concern for both healthcare professionals and patients.[3] |
| Compliance | Oral vaccine delivery is often simpler and less unpleasant, which may lead to improved patient compliance. This can significantly enhance patient acceptance, especially among children and individuals with needle phobia.[4] | The administration of injectable vaccines involves the use of needles, which can be perceived as uncomfortable or painful. This aspect may contribute to hesitancy or anxiety among individuals, particularly those who fear needles. |
| Acceptance | Oral vaccines achieve greater public acceptance, especially among children, as it is a painless strategy, thus achieving higher vaccination coverage[5] | Injectable vaccines may pose challenges for individuals with needle phobia. The fear of needles can lead to avoidance or reluctance in seeking vaccination, potentially impacting immunization rates, especially in certain demographic groups. |
| Immune response | The immune responses generated by oral vaccines may vary compared to injectable vaccines. Achieving a consistent and robust immune response across diverse populations can be challenging. The immune response elicited by oral vaccines is generally lower than that of injectable vaccines, as a higher amount of antigen is needed to trigger an immune response.[6] | Injectable vaccines generally elicit a higher immune response compared to oral vaccines.[7] |
| Adjuvants | immune response | Numerous immune adjuvants can be utilized in injectable vaccines to boost immune activity.[9] |
| Formulation Stability | Injectable vaccines enable precise dosing as the entire vaccine quantity is administered directly into the body. This dosage accuracy is critical for achieving consistent immune responses across diverse patient populations.[13] | Injectable vaccines, in contrast to their oral counterparts, bypass the challenges associated with navigating the gastrointestinal tract. The absence of exposure to the harsh conditions of the digestive system imparts several advantages to injectable vaccines, making them a preferred option under certain circumstances. Injectables offer a direct route into the bloodstream, allowing for rapid and controlled delivery of vaccine components. This ensures efficient absorption of antigens without the need to overcome barriers presented by the digestive system. This stability advantage allows for a more straightforward formulation process, ensuring the vaccine components remain intact and effective.[11] |
| Dosing | Developing oral vaccines poses a significant challenge as a higher antigen dose is needed to elicit an immune response compared to traditional injections. This constraint limits carrier choices for formulations, and the use of larger doses increases the risk of inducing immune tolerance rather than a protective response. To overcome this, the design of oral vaccine carriers is crucial, requiring potent adjuvants for effective immune system stimulation.[12] | Injectable vaccines enable precise dosing as the entire vaccine quantity is administered directly into the body. This accuracy in dosage is critical for achieving consistent immune responses across diverse patient populations.[13] |
| Versatility | Another advantage is that the patented strategy is made up of “modules” that can be assembled, thus offering great versatility for the development of new vaccines against a wide range of microorganisms using biotechnology tools applied to human and veterinary health.[14] | Unlike oral vaccines, the unique advantages of injectable vaccines lie in their ability to induce a more robust immune response with a lower amount of antigen, making them effective in triggering a protective immune response with a smaller dose compared to oral vaccines. Therefore, while the modular approach of oral vaccines is advantageous for the development of new vaccines, this specific advantage is not relevant to injectable vaccines.[15] |
| Limitations | The oral route is often more suitable for non-living or subunit vaccines, and live attenuated vaccines may not be feasible due to potential safety concerns. This limits the range of vaccines that can be administered orally.[16] | In contrast, injectable vaccines are well-suited for live attenuated vaccines and can accommodate a wider range of vaccine types, including those that may not be suitable for oral administration due to safety considerations. Injectable vaccines, by being directly introduced into the muscle or bloodstream, can effectively deliver live attenuated vaccines without the risk of degradation in the gastrointestinal tract, addressing the limitation of oral administration for this type of vaccine.[17] |
| Complexity | Developing effective oral vaccines, especially against complex diseases, can be scientifically and logistically challenging. Overcoming barriers related to mucosal immunity and achieving consistent results in clinical trials require extensive research.[18] | Injectable vaccines do not face the same challenges related to the oral delivery route. They are well-established and have been effectively used to address a wide range of diseases, including complex ones. Injectable vaccines bypass the challenges associated with oral delivery, such as surviving the harsh gastrointestinal environment and inducing mucosal immunity, making them a reliable alternative for addressing the limitations of oral vaccines in certain scenarios.[19] |
| Booster | Some oral vaccines may require more frequent booster doses to maintain immunity compared to certain injectable vaccines. This could impact the overall cost-effectiveness of oral vaccination programs.[20] | In contrast, certain injectable vaccines, particularly those containing adjuvants, are designed to provide long-lasting immunity with fewer booster doses, potentially offering a more cost-effective immunization strategy compared to some oral vaccines that require more frequent boosting to maintain protection.[21] |
| Regulatory Approval | Obtaining regulatory approval for oral vaccines can be more complex compared to injectable vaccines. Demonstrating safety and efficacy, especially with new technologies, may involve additional scrutiny from health authorities.[22] | Injectable vaccines, being well-established and having a long history of successful use, may encounter fewer regulatory hurdles compared to oral vaccines, particularly those involving new technologies or delivery methods. The extensive preclinical and clinical trials required for both oral and injectable vaccines are essential for demonstrating safety and efficacy, but the specific challenges associated with the unique characteristics of oral vaccines can contribute to a more complex regulatory approval process compared to injectable vaccines.[23] |
| Environmental Impact | The omission of disposable supplies, such as syringes and cotton wool, makes oral vaccines more environmentally friendly. This aligns with a global push towards sustainable and eco-conscious healthcare practices.[24] | Additionally, the utilization of these conventional methods results in a substantial volume of biohazardous waste, a challenge that many developing countries lack the infrastructure to manage adequately. These factors collectively contribute to elevated immunization costs, thereby posing a significant barrier to accessibility in emerging regions.[25] |
| Cost-Effectiveness | From a regulatory perspective, the production of oral vaccines holds the potential for more cost-effective manufacturing, as it eliminates the need for the extensive purification processes required in injected formulations. Parenteral injections demand a) adherence to aseptic techniques during synthesis and manufacturing, b) specialized equipment and training for healthcare personnel to ensure optimal delivery, and c) the proper use of sterile needles.[26] | From a regulatory perspective, the production of injectable vaccines involves adherence to aseptic techniques during synthesis and manufacturing, the use of specialized equipment, and the proper training of healthcare personnel to ensure optimal delivery and the use of sterile needles. This rigorous process is essential to maintain the safety and efficacy of injectable vaccines. Additionally, injectable vaccines may require extensive purification processes, specialized equipment, and training for healthcare personnel, which can contribute to the overall cost of manufacturing and regulatory approval. Therefore, while oral vaccines may offer cost-effective manufacturing advantages, injectable vaccines also have specific regulatory requirements and production costs that need to be considered |
