The role of vaccines in the post-antibiotic era
The “Post-Antibiotic Era”, a world where the antibiotics we once took for granted have lost all abilities to combat disease causing bacteria, is said to be gradually approaching us. Drugs that once prevented post-surgical infections from C-sections, cured frequently occurring infections such as the urinary tract infection and other skin and soft tissue infections, have lost their edge due to the increasing resistance of these superbugs (Baggaley, 2016). In order to prevent the possible epidemics and other uncontrollable events from arising, scientists are turning towards vaccines for the future; thus, this essay will discuss the role of vaccination in minimizing antimicrobial resistance, how existing vaccines may be able to accomplish the goal of reducing antimicrobial resistance, and finally, the future of vaccine development.
The Immune System
The immune system consists of innate and adaptive components. The innate system refers to the defense system that destroys non-specific cells. This includes phagocytes, who engulf foreign material through endocytosis (Helbert & Nairn, 2017). The adaptive system, on the other hand, are antigen-specific. This system, although highly efficient, requires an activation period of 7-10 days to be in complete mobilization. This process involves B and T lymphocytes that have specific antigen recognition molecules, which allow the cell to recognize a certain foreign organism. The antigen recognition molecules bind onto areas on the foreign entities, known as epitopes (Helbert & Nairn, 2017).
The adaptive system begins to work when an antigen invades the body, and encounters one of many unique lymphocytes which best fits the antigen, leading to its proliferation, resulting in many daughter cells. These daughter cells are clones of their predecessors, thus, there are now many more lymphocytes with receptors unique to the specific antigen. This process is known as the activation phase. Following the activation phase is the differentiation phase, this is when the daughter B lymphocytes differentiate to form plasma cells. The plasma cells are responsible for the production of antibodies, which help fight off the antigens, this process is known as the effector phase. Following the elimination of the antigens, immunologic memory develops, which means that successive exposure to the same pathogens are quickly eliminated and symptoms are reduced (Helbert & Nairn, 2017).
Vaccines
Vaccines are suspension of weakened, killed or fragmented microorganisms or toxins or of antibodies or lymphocytes that are primarily given to prevent disease (Brunson, 2018). It allows the immune system to be exposed to the specific antigen without causing infection (Michael, et al. 2014). The vaccine gains its abilities from being able to manipulate the immune system of the host organism. Vaccines may confer immunity that is either passive or active. Passive immunity provides immediate, but short-lived immunity, whilst active immunity allows for long-lived immunity (Baxter, 2007).
Active immunity occurs when the individual forms a direct response to an antigen, whereas passive immunity involves the transfer of antibody of an immunized individual to a non-immunized individual. In the context of vaccines, active immunity can occur when a weakened, killed or fragmented microorganism is introduced into the system, causing its antigen to be recognized and leading to the adaptive system beginning to work. The stimulated adaptive system produces antigen specific B lymphocytes, which now have immunological memory, allowing for quick response for future invasion of the antigen. On the Contrary, passive immunity is administered through vaccines by antibodies or lymphocytes previously made by animals or human donor (Brunson, 2018).
Antimicrobial Resistance
Antimicrobial resistance (AMR), as defined by the World Health Organization (2017), is the ability of microorganisms such as viruses, bacteria and other pathogens to stop an antimicrobial from working against it. Resistance is a natural evolutionary process, which arises from microorganisms who are more susceptible to antimicrobials surviving treatment, and passing on resistance to offspring (WHO, 2018). The combination of unnecessary use of antimicrobials by humanity, the globally interconnected population and significantly increasing AMR phenotypes presents an uprising crisis (Michael, et al. 2014). The issue of AMR has been listed by the WHO as one of the three major issues facing human health (2017). The result of resistance is the ineffectiveness of treatment; thus, the infection remains and possibly continues to spread to others. Emergence of antibiotic resistant strains has been found to be greatest in areas where therapeutic drug use is the highest per capita (Bronzwaer et al. 2002). The emergence of antibiotic resistant strains may pose a threat against the world. It has been estimated that by 2050, 10 million lives could be lost annually as a result of AMR, which exceeds the number of lives lost per year from cancer (Jansen et al. 2018). These numbers highlight the importance of finding methods in which the use of antibiotics can be reduced whilst being able to treat suffering patients.
Penicillin, the first discovered antibiotic, has been used to treat countless infectious diseases, including those caused by the bacteria, Streptococcus pneumoniae. Over the years, S pneumoniae has undergone mutations which has led to the production of – lactamases. – lactamases allows the bacteria to overpower the effects of penicillin. The resistant material is, subsequently, exchanged between more bacteria causing the spread of resistance (Jansen et al. 2018).
What roles do vaccines play in reducing AMR?
Vaccines are increasingly recognized as a valid method of reducing AMR. The use of vaccines prevents bacterial infections from occurring in the first place, thus, it mitigates the need for the use of antibiotics. As mentioned before, evidence has shown that AMR seems to be greatest in areas where antibiotic use is high, thus, a reduction in the use of antibiotics will consequently lead to reduced development of antibiotic resistant strains (Lipsitch et al. 2016).
Another way in which vaccines are strong contenders of methods used to reduce AMR, is herd immunity. Herd immunity occurs when vaccines are broadly administered in a population which not only allows the vaccinated individuals to be immune to the disease, but it also protects those who were not able to get vaccinated due to individual conditions, such as chemotherapy (Jansen et al. 2018).
To summarize how existing vaccines could possibly be beneficial, in the context of AMR, one can imagine an individual who has been vaccinated against infection A. In scenario 1, the patient does not get infected by the pathogen and is not prescribed antimicrobials, thus there is no possible “poor outcome”. In scenario 2, the patient does become infected, but due to the previously administered vaccines, infection A does not colonize the individual. This leads to several outcomes which are ideal for the reduction of AMR; due to the infection not colonizing, there is a reduced population of the pathogen, therefore, it minimizes the opportunity for the resistant material to be exchanged. Another outcome is that there is a lower rate of transmission to other individuals, both vaccinated and unvaccinated, leading to herd immunity (Lipsitch et al. 2016).
[Image source: Lipsitch et al. 2016]
How are existing vaccines reducing AMR?
One of the most common, highly contagious cause of respiratory illness is the Influenza virus. This virus is known to cause the common respiratory illness known as the flu (CDC, 2018). The flu is known to cause 5 million cases of severe illness annually, where 250,000-500,000 cases result in death. The morbidity of this illness is increased by secondary infections, which occur during or after an infection by another pathogen. Secondary infections as a result of the influenza virus includes pneumonia, caused by the infection of the bacteria, Streptococcus pneumoniae (Morris et al, 2017). The Influenza virus can be treated by both antibiotics and vaccines (Haemophilus influenza type b or Hib vaccines). Antibiotics have been commonly used to treat this illness, however, often times they have been prescribed inappropriately. During the period of 2005-2009, of the 270,057 individuals who had contracted influenza, 58,477 were prescribed antibiotics. Of those individuals who had been treated with antibiotics, 79% did not suffer secondary infections, this indicates that there had been a large number of unnecessary antibiotic prescriptions. The abuse of antibiotics leads to increased AMR (Esposito et al. 2018). Since the early 1970s, a steady increase of AMR strains of the influenza virus had been observed, the number of AMR strains which were tested positive for – lactamases (protein which allow for AMR) eventually reached 16.6% of total influenza strains worldwide tested. The administration of Hib vaccines, on the other hand, decreases the possibility of infections. The use of Hib vaccines prevents secondary bacterial infections, including pneumonia, hence, lessening the need for antibiotics. Another secondary bacterial infection as a result of the Influenza virus is otitis media. In Turkey, children who had been vaccinated against Influenza experienced a 50.9% reduction in chances of suffering otitis media (Morris et al, 2017). The beneficial effects of the Hib vaccine has also been observed in Canada; where the introduction of Hib vaccinations in 1988 led to a staggering decrease in cases of influenza per 100,000 people, which dropped from from 2.6 to 0.08 (Jansen et al. 2018). This decrease consequently led to reducing the need for antibiotics, thus limiting the increase of AMR (Esposito et al. 2018).
The Development of New Vaccines to Combat AMR
There is a significant number of bacteria and pathogens which are continuously undergoing mutation of different forms, leading to AMR. The problems that are tied with the inability of existing antibiotic treatment of the infections caused by these microorganisms vary in severity. The World Health Organization has therefore identified a list of critical, high and medium priority pathogens which are in need of new antibiotics that could be used for treatment (2017). However, the use of antibiotics to treat these already multi drug resistant pathogens seems to be a short term solution, which is why this essay will cover the vaccine development process of one of the 3 critical priority superbugs.
Acinetobacter baumannii has been named one of the three critical pathogens in immediate need of new antibiotics for treatment due to multi-drug resistance by the WHO (2017). The bacteria targets exposed moist skin, causing the skin to resemble the skin of an orange. If the infection is left untreated, complications could lead to septicemia, which is the infection of blood by bacteria, more commonly known as sepsis (Medline plus, 2018). The severity of the increasing AMR of this bacteria is emphasized by the bacteria becoming increasingly common amongst soldiers in Iraq, where high numbers of septicemia cases have been recorded as a result of A. baumannii infection. In France, researchers identified one A. baumannii strain which has been found to have a staggering mortality rate of 26% in infected individuals (Howard et al, 2012). The progression of the severity of the AMR of this bacteria has caught the attention of scientists, whom have begun a brief, yet critical discussion of the development of vaccines for this specific pathogen. It is said that the production of vaccines is possibly the most cost efficient strategy of defense against infections (Chiang et al, 2015). A. baumannii vaccines are challenging to produce as there is very little discussion about the continuously increasing success of these bacteria as pathogens in humans (Mcconnell et al, 2013). The development of vaccines begin with the choice of specific antigens on the bacteria membrane who have vaccine potential. The criteria for such antigens includes being expressed on the outer membrane or secreted as virulence factors, contain protein sequences or protective epitopes highly conserved among A. baumannii strains, and play an important role in pathogenesis during infection (Chiang et al, 2015). The immunogenicity of the antigen is of great importance in the development of vaccines. Immunogenicity is the consequence of the administration of biopharmaceuticals, the body may recognize it as a foreign substance and initiate an immune response without correctly stimulating the desired response and thus not having the appropriate results. Low immunogenicity leads to increased removal of the substance from the system which may cause an overestimation of the safety of the biopharmaceutical during trial period (Faqi, 2011). In order to increase immunogenicity, the genes of the identified antigens are used to form recombinants. The recombinants are then used to immunize blood samples from mice. The immunized blood is later tested for the presence of an antibody response, which would indicate the functionality of the antigen as a possible vaccine (Chiang et al, 2015).
Conclusion
With increasing AMR found in various microorganisms, as a result of natural evolutionary processes and sped up by the abuse of antibiotics, the threat of a possible incurable epidemic to the human population is escalating. As vaccines decrease infectious diseases, it will significantly reduce the need for antibiotics which is then proven to reduce AMR. Therefore, I believe vaccines are a vital component in reducing AMR. because Canada, as an example, has shown a positive outcome of decreased infection rates of the influenza virus following implementation of vaccines. This argument is further strengthened by the evidence shown in Turkey, suggesting that vaccines reduce secondary infections, thus lessening the need for antibiotics. Finally, the development of future vaccinations is vital at this stage due to the increasing number of multidrug resistant superbugs