Vaccine Development, Advantages, and Disadvantages of Group Immunity and Future Perspective for COVID-19

Abdullah ¹, Maqsood ur Rehman¹, Fazlullah Khan^{2, *}, Tapan Behl³

¹ Department of Pharmacy University of Malakand, Chakdara Dir Lower, Pakistan

² Department of Allied Health Sciences, Bashir Institute of Health Sciences, Bharakahu, Islamabad, Pakistan

³ Chitkara College of Pharmacy, Chitkara University, Punjab, India

Abstract

Since its outbreak in late 2019, SARS-CoV-2 has infected millions of people and caused 432, 204 deaths across the globe up to June 14, 2020 (WHO website). SARS-CoV-2 has a high transmission, prolonged incubation time, and an increased prevalence of asymptomatic infection. All over the world, the authorities are insisting on non-pharmaceutical interventions such as social distancing, imposing lockdowns, social isolation, and provision of personal protective equipment (PPEs) to the hospital and other essential departments. However, these measures have only slowed down the virus and cannot prevent rebounds on easing the restrictions. Moreover, the hype about the off-label use of drugs is on the rise. However, the efficacy and the risk of adverse effects have yet to be explored in clinical trials. Therefore, the only way to confer immunity and control the pandemic, the development of vaccines, is currently the research focus. The genetic sequencing of SARS-Cov-2 was done quickly, only in one month. To develop vaccines at pandemic speed, the scientific community faces the challenge of proof of clinical safety and efficacy. Moreover, the previous work is done, and scientists are utilizing the experience of SAR-CoV and MERS and the technologies thereof for COVID-19. Several manufacturers have announced their program and progress on vaccine development. Some vaccines have cleared phase I, and phase II clinical trials, while few are in phase III.

Keywords: Clinical trials, Coronavirus, COVID-19 vaccines, Group immunity, Herd immunity, Vaccine candidate.

^* Corresponding author Fazlullah Khan: Department of Allied Health Sciences, Bashir Institute of Health Sciences, Bharakahu, Islamabad, Pakistan; Tel.: +92 346 9433 155; E-mail: fazlullahdr@gmail.com

INTRODUCTION

Historically, vaccination is the most efficient countermeasure against infections, as the administration of pathogen-resembling agents increases the immune response against the invader. Vaccine technology continuously progressed in emerging viral threats to promote immune response [1, 2]. The development of vaccines is more time-consuming and complicated, which is different from the conventional medicine development process. Vaccine development usually takes 12-15 years [3]. Conventional medicines are used to treat disease whose symptoms have appeared, while vaccines are being used for a disease, the symptoms of which are yet to occur [4]. Clinical trials evaluate the effectiveness of vaccines and determine their ability to prevent disease with minimum adverse effects [5].

COVID-19 vaccines are initially tested in mice/rabbits for assessment of safety. Testing in humans is initiated after the animals do not exhibit signs of disease after administering the vaccine. The number of subjects is gradually increased with advancing stages of clinical trials to detect rare adverse effects. Before the approval of general-purpose vaccines, thousands of vaccinated people are followed for several months [6]. If the vaccine results in malfunctioning of the immune system or causes severe inflammation, the vaccine may not be suitable for widespread use. Delay in vaccine development is inevitable when such adverse effects are detected [7].

The term “herd immunity” was introduced almost a century ago and is now widely used after increasing vaccines for the eradication of disease [8]. It is also known as group immunity or community immunity. Herd immunity is achieved when a large portion of the population is immune to a specific disease, protecting the susceptible individuals indirectly. The higher the portion of the population that is immune to a disease, the lower the chance for a susceptible individual to contact an infectious person. If many people (herd) are immune, the circulation of infection in the community will stop. Herd immunity should be in more than 80% of individuals to confer protection upon susceptible individuals [9]. This percentage is different for different pathogens depending on the contagiousness of pathogens. Higher the contagiousness of pathogen, a more significant portion of the population must be immune to provide herd immunity. For example, in SARS-CoV-2, the percentage of the people needed for herd immunity is 70% [8]. If the fraction of susceptible individuals in a population is too few, then the pathogen cannot successfully spread, and its prevalence will decline. Herd immunity threshold is the point at which the proportion of susceptible individuals falls below the threshold required for transmission [10]. Sensitive individuals take benefit from indirect protection from infection above the herd immunity threshold. The benefits of herd immunity imply various segments of the population. For example, it is useful to protect immuno compromised individuals who cannot be vaccinated. It includes elders who cannot exhibit an optimal immune response to vaccines, children too young to be vaccinated, individuals having no access to mass immunization, and people who do not get vaccinated [10].

For COVID-19 vaccine efficacy, immune deficiency is a risk factor, especially in elders whose immune system has already been weakened by many factors. Moreover, obesity also results in the weakening of the immune system. It occurs due to lower IgG levels and a higher level of IL-6. Respiratory infections and infections caused by parasites also affect the immune response to COVID-19 vaccines [11]. Research on SARS-CoV and MERS has helped scientists to unveil the mechanism of protection offered by the immune system against the disease and the human body's response to coronaviruses. In pandemic situations, hundreds of millions of vaccine doses are required, which, if already production lines are available, are manufactured in about six months. A new vaccine needs several quality control checks because the unique production process is involved [12]. This chapter aims to summarize the development of vaccines for COVID-19 and the advantages and disadvantages of group immunity.

Clinical-Phase Vaccine Candidates for COVID-19

Several strategies are adopted for COVID-19 vaccine development; most of these target S proteins as the primary inducer of neutralizing antibodies [13]. The S protein molecule has S1 and S2 subunits. Subunit S1 contains a receptor-binding domain (RBD) which interacts with the host cell receptor (ACE2). The S protein plays a crucial role in inducing protective immunity during infection with SARS-CoV by eliciting T-cell responses and neutralizing antibodies. In contrast, the subunit S2 facilitates the fusion of the virus with the host cell membrane to release the viral RNA into the cytoplasm for replication [13]. Hence, vaccines based on S-protein should induce antibodies that block virus genome uncoating as well asnd viral receptor binding. Thus, the whole S glycoprotein or its appropriate parts are considered the key candidates for the vaccine composition of CoVID-19 [14].

Up till now, no vaccine is licensed to prevent human respiratory infection. About 10 COVID-19 vaccine candidates are in different stages of development, as shown in Table 1 [15]. The main criterion for a vaccine is safety, efficacy, and duration of immunity. The pandemic vaccine needs high production capacity and rapid development. This limits their rapid deployment during pandemics. Furthermore, live attenuated coronavirus vaccines are produced by reverse genetics from infectious virus clones by deleting multiple key virulence determinants to prevent reversion. It remains the most immunologically robust, inducing systemic, mucosal, cell-mediated, and humoral immunity and broader cross-protection [15^-17].

Table 1 COVID-19 candidate vaccines – June 9 2020 [27].

A clinical trial for a new DNA vaccine against coronavirus (ChAdOx1) aimed against MERS, has started [18]. This vaccine is based on the spike protein of SARS-CoV-2 and the adenovirus as a vaccine vector [19]. It has been modified such that the genetic code sends instructions for spike protein production that allows the production of this protein by adenovirus after vaccination. Thus, antibodies are produced against spike protein [20]. The University of Oxford, UK is striving to develop a chimpanzee adenovirus vector (ChAdOx1 nCoV-19) based COVID-19 vaccine. It encodes the spike protein of SARS-CoV-2. It is tested in phase II and III trials for tolerability, safety, reactogenicity, and immunogenicity profile. ChAdOx1 is a non-replication vaccine vector and stimulates both sides of the adaptive immune response, including cytotoxic T-cells and humoral response. It has exhibited efficacy in several clinical trials, including those for Zika, Chikungunya, and MERS, and is also being tested as a cancer vaccine platform [21].

Traditionally, inactivated purified viruses have been used to develop vaccines that are safe and effective for the prevention of diseases caused by polio and influenza virus [22, 23]. This technology is being utilized by the Institute of Medical Biology, the Chinese Academy of Medical Sciences, and the Beijing Institute of Biological Products to develop vaccines for COVID-19.

Protein subunit vaccines are obtained either by recombinant DNA technology or by conventional cultivation methods. It contains only certain antigenic determinants of pathogenic microorganisms [24]. The antigenic determinants enhance the efficiency of immune response, and the risk of side effects is reduced by the presence of a small number of pathogens. The antigens are conjugated with protein molecules to obtain vaccines of strong immunogenicity [25]. DNA vaccines have the advantage of high stability and stimulating both humoral and cellular immunity. Its other benefits are that it confers long-term immunity, and the plasmid can be manufactured in large amounts [26].

Diversity of Technology

Scientists across the globe are struggling hard to search for potential techniques to develop efficient vaccines against COVID-19. Neutralizing antibody production against the spike protein (S) and the blockade of ACE2 receptor is the key target for the majority of COVID-19 vaccine candidates [28, 29]. The prominent feature of COVID 19 vaccine development is the diversity of platforms under investigation.

The conventional approach to developing COVID-19 vaccines may be the application of attenuated or inactivated strains of SARS-CoV-2. Still, these have disadvantages, including a long duration for sufficient material production, the risk of re-acquired virulence, and adverse effects [30, 31]. A safer and quicker method is subunit vaccines based on individual proteins, which may be administered in combination with adjuvant or VLPs. Currently, it is used for the development of vaccines against SARS-CoV-2. All the structural proteins of SARS-CoV-2 are immunogenic and can produce CD4+/CD8+ T cell responses [32]. However, studies have indicated that antibodies against N protein do not provide protective immunity while E and M proteins provide a weak protective response [33]. The virus-like particles (VLPs) lack the viral genome. It may be an alternative platform of inactivated or attenuated vaccines as it has no reactogenicity and reversion to pathogenic forms [34, 35].

Nucleic Acid (DNA and RNA)

Several platforms are under extensive research to develop COVID 19 vaccines. Out of these, nucleic acid-based platforms have the most significant potential because these require a synthetic process and do not need fermentation or culture [36]. That’s why even just after 2 months of SARS-COV2 sequence identification, Moderna started testing its mRNA-based vaccine mRNA-1273. The mRNA vaccines are directly administered into the cells to produce antigens in vivo. Once translated, the antigens are transported extracellularly for antibody recognition and presentation to T cells and immune response [36, 37]. It has the advantage that as the antigen is produced in vivo. The natural immune response is achieved. However, it has the disadvantage of being unstable and inefficient in vivo delivery of mRNA [38].

Similarly, DNA vaccines are administered extracellularly to express antigens in vivo. DNA-base vaccines are more stable and induce more prolonged antigen expression. Therefore, it confers a long-lasting immune response compared to RNA vaccines [39].

Virus-like Particle

It consists of the structural proteins of the virus assembled to form a particle. These are non-infectious and large but still heterogeneous antigenically. It combines the best traits of whole virus vaccines and subunit vaccines. Structurally, virus-like particles resemble infectious viruses; therefore, they can induce potent cellular and humoral response without adjuvant use [40]. The particulate nature of virus-like particles makes them capable of inducing potent T cell-mediated immune responses by interaction with antigen-presenting cells, particularly the dendritic cells. Due to their enhanced efficacy compared to subunit vaccines, the virus-like particle garners high scientific interest as vaccine candidates [41]. The high pathogenic nature and contagiousness bring great difficulties in SARS-CoV-2 related research. Therefore, VLPs provide a better alternative to study SARS-CoV-2 vaccine efficacy in the lack of suitable animal models [42].

Peptide

No peptide vaccine has yet been approved for use in humans. The first peptide vaccine was designed for canines. Several studies have exhibited that peptide vaccines are pretty effective, especially in cancerous tumors. It has been reported that traditional vaccines require more time and money than peptide vaccines [43].

The pathogen-derived antigens (spike protein in case of COVID-19) are used to elicit an immune response. The spike glycoprotein induces the highest neutralizing antibody titers. It is a promising candidate for the development of vaccines [44, 45]. But the peptide vaccines developed for SARS and MERS were partially effective in protecting viral challenges in animals. They were unable to elicit an immune response that occurred in natural infections. One of the many reasons for this failure could be that peptides are just a portion of the virus [46].

The advantages of peptide vaccines are their easy manufacturing process and storage, while the demerits are limited global production capacity, require adjuvants, and poor immunogenicity [47]. Nevertheless, Most of the peptide vaccine candidates are based on spike protein with the addition of an adjuvant to improve immunogenicity. For instance, Innovax plans to study several truncated spike proteins in pre-clinical trials to select a lead candidate from the resulting immunogenicity data that will further be evaluated with oil in water adjuvant [47].

Live Attenuated Virus

These vaccines are the most immunogenic but carry the risk of becoming pathogenic after mutation. Moreover, the inactivation of the whole virus is carried out via different chemical and physical means that turn the virus “dead”. Yet, its immunogenicity is intact. In this technique, a modified live SARS-CoV-2 virus having reduced virulence (e.g., mutated E protein or codon deoptimization) is used [48]. Its advantage includes all of the virus's natural components such as nucleic acids, proteins, glycans, and lipids, thereby eliciting a potent immune response and outperforming other vaccine development strategies. It may require just a single dose and are self-replicating [49].

Viral Vector (replicating and non-replicating

Engineered non-pathogenic viruses carry the genetic material of another virus and deliver it into cells to produce antigen in vivo. The adenovirus and measles virus is commonly used vectors. Like nucleic acid vaccines, viral vector technology may be modified to express the antigen of choice. Moreover, this technology delivers the genome intracellular, doesn’t rely on adjuvant, and can induce a robust T-cell response [50].

Adenoviruses are the most commonly employed vectors for vaccine development. Its molecular biology and virology have been investigated for many years as a tool for gene therapy applications, thus, providing sufficient knowledge for vaccine development [51]. The deletion makes adenovirus non-replicating of genes from the area responsible for replication (E1 region). Furthermore, to increase space for the foreign genes, the E3 region genes are also deleted. The most extensively exploited adenovirus used as a non-replication vector is adenovirus 5. The replicating adenovirus has its E1 region intact, which has the advantage of dose sparing i-e little amount is required because the vaccine vector replicates in vivo. Adenovirus 4 and 7 are commonly used as replication-competent vectors [52].

COVID-19 vaccine (ChAdOx1 nCoV-19) encoding the SARS-CoV-2 Spike protein, being developed by the University of Oxford, UK, is based on a chimpanzee adenovirus vector [53]. ChAdOx1 is a non-replication vaccine vector and stimulates both wings of an adaptive immune response, including cytotoxic T-cells and humoral response, has demonstrated efficacy in various clinical trials [54]. Viral vectors-based vaccines exhibit long-term stability and a high degree of protein expression and thereby induce a strong immune response [55].

Recombinant Protein

Although all the four structural proteins of SARS-CoV-2 such as spike, nucleoprotein (N-protein), membrane protein (M-protein), and envelope (E-protein), can be the targets for vaccine development. The high immunogenicity of the S protein makes it the best candidate for the development of the vaccine [48]. Moreover, the S vaccines preclude the interaction between SARS-CoV-2 and ACE2 and thus prevent/bring to halt COVID-19. SARS CoV2 proteins (S protein) are administered to the host to elicit an immune response. An adjuvant is also co-administered to increase immunogenicity. Recombinant protein vaccine candidates can benefit from the already existing large-scale production because such vaccines have already been licensed for other diseases [56].

Monoclonal Antibodies (mAbs)

Passive immunization with mAbs causes a reduction in virus replication and spread. It has been demonstrated in several studies that these antibodies are effective in the treatment/prevention of highly pathogenic viral diseases via neutralization of structural proteins of the virus [57, 58]. In vivo and in vitro studies evaluating the use of mAbs against SARS and MERS blocked the replication of viruses and improved the clinical condition of patients. Moreover, the inhibition of the virus was explained with the use of antibodies against MERS-CoV glycoprotein S after 24 hours of infection in a humanized dipeptidyl peptidase 4 (DPP4) receptor mouse model [58].

Inactivated Virus

Purified inactivated viruses have been traditionally used for the development of vaccines. Such vaccines are safer and effective in preventing infections caused by influenza and poliovirus [22, 23]. In a study carried out in China, the SARS-CoV-2 vaccine candidate has resulted in neutralizing antibodies in non-human primates, rats, and mice. A clinical trial (Phase 1/2) is in progress on 744 humans participants [23]. Inactivated virus vaccines have the advantage of the requirement of single-dose; have a broad and potent immune response. However, it has some disadvantages like these are less immunogenic as compared to the attenuated vaccines. It has to be supplied in dry form to make the structure more stable, requires a separate solvent supply, and be transported in a cold chain. These steps increase the production cost of the vaccine [58].

Clinical Trials in Terms of Vaccine Development

Clinical trials are research studies on human volunteers to evaluate the safety and efficacy of treatment products or preventative measures such as medicines or medical devices, and vaccines. It provides deeper insight into vaccines that can help prevent diseases. Clinical trials are a critical step to get approval from regulatory bodies of vaccines or medicines and medical devices [45]. An individual novel vaccine must be assessed for its immunogenicity, safety, and effectiveness before it is licensed for human use. After discovery, every novel vaccine endures an extravagant development process. The vaccines must pass some clinical trials before launching for human use, including toxicity, an immunogenetic response in adults, chances of acceptance by the community, possible impact on public health, cost-effectiveness, and benefit to risk ratio.

Looking to this fast drive of COVID-19 vaccine candidates into human trials, the time it takes to develop vaccines for this evolving pathogenic microorganism is reducing compared with other vaccine candidates of the past. They are generally used as traditional infantile vaccines. Lately, a DNA-based vaccine candidate for the novel SARS or original SARS, i.e., SARS-CoV-1, was developed in one. A half-year vaccine for H-5 influenza A in almost one year (approximately 11 months) in Indonesia in 2006, another vaccine candidate for H-1 influenza A took just four months to develop at California USA in 2009. Similarly, a vaccine candidate used against the Zika virus was developed in just three and half months [59]. These accomplishments have been carried out by modern skills, innovative technologies, and advanced approaches that have allowed for the rapid identification and sequencing of new and emerging pathogenic viruses and the latest technologies for vaccine candidate delivery [59]. For the past 15 years, the HIV vaccine arena has founded the development and usage of recombinant DNA or recombinant antibody technology. It is novel animal models (in-vivo studies), cutting-edge computational methods, and advanced vaccine delivery methods with new approaches to fast-track HIV vaccine immunogen development, design, and delivery [60^-63]. The timeline for a COVID-19 vaccine candidate will probably be much faster. It is even much easier than for other vaccine candidates of the past. Investigators, researchers, and scientists have worked to assimilate these iterative aspects and approaches for vaccine development and antibody countermeasure development and apply them to a quick response to the COVID-19 pandemic.

Clinical trials are needed to be designed based on some parameters to get the required data: • Product to be investigated • Methods by which the trial will be conducted •Goals or endpoints • The population to be studied • Double Blinding [64]. Randomization is a method in which study participants are placed in different treatment groups based on chance. Different treatments in similar groups are comparably tested by researchers using randomization [65].

Several organizations, including BioNTech/Fosun, Moderna/NIAID, and Pharma/Pfizer, are now developing vaccines/medicine to prevent COVID-19. These candidates use several mRNAs with lipid nanoparticles or DNA. For example, “Inovio” vaccines, nanoparticles, attenuated viruses, proteins, and viral vectors carrying SARS-CoV-2 viral genes as vaccine goes through immunogenicity and safety trials. A lesser number of vaccine candidates will be tested in phase III clinical trials or efficacy trials to determine its effectiveness and safety. On the other hand, presently, with Phase I and Phase II clinical trials, it is significant to develop the capacity for large-scale vaccine production in a successful efficacy trial [66, 67]. It is possible that genetic immunization techniques such as mRNA in LNPs or DNA can be manufactured quickly as compared to viral vectors or proteins and may be more economical [68].

Preclinical Research

Identification of vaccine candidates is made through pre-clinical evaluations, which may involve selecting proper antigens to elicit an immune response and high throughput screening [69]. Appropriate drug formulations (i.e., injection, tablet, etc.) and approximate dose ranges are determined during the pre-clinical stages. Before moving to the phase one trials, the vaccine candidate may be first tested in laboratory animals in pre-clinical research. For testing of adverse effects and immunogenicity, the oral polio vaccine has been first tested in non-human primates and monkeys [70]. Determination of the immunological response to the vaccine and its safety, such as toxicity, are necessary components of the pre-clinical stage [71]. Conventional drug trials focus on pharmacokinetics and pharmacodynamics. It is mandatory to determine the interactions with the immune system and toxic effects at all possible dosage levels during vaccine trail [72].

The vaccines were not always as pure as possible to prevent adverse effects due to a lack of regulations on pharmaceutical manufacturers. Vaccine trials and manufacturing must be handled cautiously to avoid infecting the recipients or causing adverse effects. Since the Cutter Incident, the public has not gained the same confidence level in science and vaccines, which risks public health for everyone [73].

Structural determination of the principal targets of antibodies to counteract, e.g., the spike protein in SARS-CoV-2, Env in HIV, and hemagglutinin in influenza A, has provided a valued atomic-level image develop strategies for the vaccine (s). Especially, cryo-electron microscopy has enabled the rapid solution of the structure of the SARS-CoV-2 spike protein [74, 75]. The supercomputer combines different fields and aspects, including computational biology, structural biology analysis of viral pathogens cartels structural, biophysical, and biochemical approaches to comprehend the interactions of pathogenic virus or other microorganisms with the human immune system [76^-79]. It can be implemented for the production of the COVID-19 vaccine, as shown in Fig. (1). To accelerate structure-based vaccine design for COVID-19, recently, structural biologists spun to apply technology developed for respiratory syncytial virus (RSV) or HIV-1 envelope structural biology [74, 75, 80, 81]. Presently, recognized pipelines for high-resolution cryo-EM determination of the structure of the SARS-CoV-2 spike are unified with the computational teams with the help of a supercomputer, consequently providing atomic-level feedback to SARS-CoV-2 (COVID-19) vaccine designs.

HIV-1 antibody discovery in the recent past has provided patterns for HIV-1 vaccine candidate design and development, which aimed to provoke broadly reactive neutralizing antibodies [82, 83]. It has become clearer that an effective vaccine will likely require multiple immunogens administered in a specific order. It has facilitated proper antibody development to multiple neutralizing targets on HIV from the contemporary literature available for the ontogeny of HIV neutralizing antibodies [62]. Expectantly, the development of SARS-CoV-2 neutralizing antibodies against COVID-19 disease will necessitate a much simpler vaccination regimen like that of the vaccine developed against the Zika virus, where only a single immunization with a single antigen was enough to induce protective neutralization of antibodies [84]. This kind of vaccine would be suitable for fast-track development, large-scale manufacturing with global administration to mankind.

Fig. (1))

Schematic Diagram of vaccine Development for COVID-19 supercomputers assisted research on COVID-19 vaccine.

Non-Specific Vaccine

There is evidence of the effectiveness of the BCG vaccine in respiratory infections, but the duration and magnitude of these non-specific effects are unknown at present. Therefore, implications on practice and policy on the BCG vaccine cannot be determined [96]. The WHO has explained that evidence-based recommendations currently do not justify changes to the current global immunization policy [96]. There is systematic review evidence with low to moderate risk of bias that BCG vaccination prevents respiratory infections (influenza and pneumonia) in elders and children. BCG vaccine modifies humoral responses to influenza and pneumococcal vaccines. More extensive research is required to study the duration and magnitude of the non-specific effects of the BCG vaccine on mortality of any cause before considering implications for policy and practice. At present, there is no evidence that the BCG vaccine provides protection against COVID-19, and caution should be exercised when interpreting and studying their correlation. It is too early to jump to immature conclusions being still during the COVID-19 pandemic, where COVID-19 cases/deaths may still increase over time in some BCG-using countries. Good evidence should be obtained from prospective randomized trials before reflecting on practice and policy [97].

Group Immunity

Protection from the disease in a group, due to a large enough proportion of the population having immunity to prevent the disease from spreading from person to person” [98]. When the majority of people in the community are immune to an infectious disease, let leads to provides in-direct defense (herd immunity). It is also called herd protection, e.g., if 75- 80% of people in the community are immune to a specific virus, 4 out of 5 people who meet or contact with someone having the disease would not get ill and so would not be able to spread the disease further. In this fashion, the spreading of infectious diseases can be kept under control. Depending on how transmissible it is, typically, 70%-90% of people require immunity to attain herd immunity. There are several diseases (Measles, mumps, polio, and chickenpox, etc.) that were once very common, but now these diseases are sporadic across the globe. This reduction or even eradication of these infectious diseases was possible because of the development of the vaccine. It provided herd immunity against these diseases. Sometimes outbreaks can be observed for vaccine-preventable conditions, particularly in lowered vaccine coverage communities due to lake of because of herd immunity.

Infectious diseases have no vaccine. Even if most people have attained immunity because of the previous infection, the disease can still spread among the communities, especially the children and the people with poor or less developed immune systems. This was observed in the past for several diseases before vaccines were developed for them.

COVID-19 is also similar to other coronaviruses that are presently spread in the whole world. Due to mutation with time, antibodies from a prior infection can give protection for a short period only. Therefore, we can expect that all those who get infected and recovered from COVID-19 would be immune for few months to few years, but most possibly not to be immune for their whole lives.

Herd Immunity and COVID-19

There are only two ways to get herd immunity: 1. Majority of the population, i.e., 80%, either get an infection and then recovered, as discussed earlier, or 2. The vaccine can protect them. According to the literature available on coronavirus infection, we require at least 70% of the population to be immune to get herd protection. If social distances and other means of contact are not reduced, the disease can spread within a few months. According to Imperial College London, this would defiantly devastate the hospitals and leads to a high mortality rate. In the finest case, we can uphold current levels of disease or can decrease the level until the availability of a vaccine [99]. According to the instruction, this is only possible to follow SOPs by keeping physical distancing for a prolonged period, probable for one year or even longer. Sometimes people exposed themselves intentionally to achieve immunity. This was done before the development of varicella vaccines. This approach might be reasonable for less severe diseases. But this method can not be applied in SARS-CoV-2 as it carries a much higher risk of severe disease and even death. Scientists are striving furiously to develop an effective vaccine. Meanwhile, as most of the population is not infected by SARS-CoV-2, some preventive measures are required to prevent explosive outbreaks like those we have seen in places like New York City [99].

Advantages and Disadvantages of Herd Immunity

There are lots of people who only depend on herd immunity to protect themselves from COVID-19. These people are mainly susceptible to diseases. The following are groups of people who need herd immunity: people living without the spleen as they have no completely functional immune system; Patients who have cancer and are under chemotherapy treatment; patients who have HIV/AIDS; neonates and old age people. The main advantages of herd immunity include the complete elimination of infection, reducing the hazard of disease for those who can’t take vaccines due to contraindication, and last the people who refused to take vaccines [99]. On the other hand, herd immunity has some disadvantages: herd immunity applies only to contagious diseases and raises the average age of infection among those infected (e.g., polio, rubella, and varicella), etc.

FUTURE PERSPECTIVE OF VACCINE DEVELOPMENT

Usually, herd immunity is not achieved in one or two years to prevent the spread of disease, and vaccine development may take a decade or more based on its ability to prevent disease in tens of thousands of people [100]. Therefore, based on the emergency of the COVID-19 pandemic, the FDA may accelerate the standard process of vaccine approval and grant approval for the emergency use of vaccines. In such a situation, when the vaccine has exhibited safety and efficacy to get an immune response in a high percentage of people. The authorities may prioritize high-risk individuals such as health care professionals/workers who will serve as a test case to determine how well the vaccine protects people from COVID-19 [101]. Moreover, mass immunization up to about 70% of the population may take years. Moreover, to provide vaccines to the general public, the biopharmaceutical industry will need a herculean manufacturing effort.

The development of vaccines for human use can take years, particularly when new technologies are being used which have not been extensively tested for safety or scaled up for mass production. As no coronavirus vaccines are available and no large-scale manufacturing capacity exists for these vaccines, there is a need to build processes and capacities. It can be tedious and time-consuming for the first time [102].

CONCLUSION

Scientists started developing vaccines for recent outbreaks of coronavirus (SARS-CoV, 2002 and MERS, 2012) but were not materialized for many reasons. COVID-19 outbreak is more severe and broad, and according to some researchers, the disease may become seasonal and endemic. Therefore, many companies and researchers are working to develop a vaccine against SARS-CoV-2 throughout the world. A varied range of technological platforms is being evaluated for vaccine development, including live attenuated virus, inactivated virus, nucleic acids (RNA and DNA), peptides, virus-like particles, recombinant proteins, monoclonal antibodies, and viral vectors. As there is no treatment available to cope with COVID-19, the social distancing and lockdown harm the economy of the world. Therefore, there is a dire need for vaccines across the globe. The speed of research is unprecedented, and it is hoped to get the vaccine soon.

CONSENT FOR PUBLICATION

Not Applicable.

CONFLICT OF INTEREST

The authors confirm that this chapter contents have no conflict of interest.

ACKNOWLEDGEMENT

Declared none.

REFERENCES