COVID-19 and Developments in Vaccinology

Abstract

With the high transmission and massive impacts of Covid-19, governments have made efforts to curb its effects. The like measures have focused on moderation and containment, conveying various degrees of success and failure. Nations have maintained the spread of covid-19 through social distancing, covid-19 testing, strict quarantine, contact tracing, and mass testing. The scale of data administration and organization for effective implementation of approaches has-in many prosperous nations depended on adopting digital technologies and integrating them into healthcare. Perhaps, these viewpoints guarantee a framework for pandemic response and management while stating how governments have embraced Surveillance, Testing, Quarantine, Contact Tracing, and healthcare terminology.

Introduction

Covid19 infected more than 100 million people, and about 2 million people died from the disease. There are still high risks of the disease to the elderly. So the need for safe and effective vaccines has risen. Notably, the severe acute syndrome Corona Virus-2 (SARS-CoV-2) was the contributory facet of the covid-19 infection⁴. The natural source of the infection was a bat, and the viruses can be transmitted to humans and animals after mutations. On March 11, 2011, the World Health Organization affirmed the virus as a global health concern due to its rapid and high potential to spread globally. The disease prevailed in Middle East respiratory syndrome and acute Respiratory Syndrome outbreaks⁴. The increased value indicated a rapid growth even with the set international prevention measures, including the closure of social gatherings, social distancing, lockdowns, and quarantines. Therefore, it accelerated the need to develop mass manufacture of vaccines against SARS-CoV-2. Mainly these vaccines are driven by both traditional and future platform terminologies. Ideally, a successful vaccine would have to vulnerable people with no future impacts on their health. They are considered the most significant in modern medicine by creating the immune before one’s infection and weakening the active parts of already existing organisms in a person’s body. Besides, some vaccines go beyond safeguarding one’s body from other related diseases to the subject infection. However, while Covid-19 vaccines convey tremendous benefits to individuals’ bodies, whether taken or injected before infection or when one is already infected, there is a debate about their vaccination development and future safety to individuals’ bodies. This entails analyzing the Covid-19 development stages and technologies, discussing their efficacy and feasibility, justifying their overall benefits, ethical issues, and biological limitations, and recommending the best technology.

Covid-19 vaccine development technologies

Researchers argue that appraising a new vaccine to society incorporates numerous stages, including clinical trials, vaccine development, food, and Drug Administration (FDA) approval, production, and distribution. Private and public organizations have worked on the development technologies of Covid-19 vaccines to bring a solution to the public¹. It entails the initial development of the vaccine at the laboratories. Scientists develop the procedures and practices of a particular vaccine in the laboratory. After initial practicals and development, they undergo three clinical trials to certify they are harmless and operational. The three steps of clinical trials take place simultaneously, making necessary adjustments for various vaccines; however, during the development of covid-19 vaccines, these phases speed up the process¹. This was done to get vaccines to people who needed them and keep the epidemic under control. No trial phases were skipped; the tests involved many volunteers of varying races, ages, and ethnicity. The trials compared thousands of outcomes and indicated their effectiveness against severe infections and death.

The preclinical and clinical trial development includes animal models and tests. SARS-CoV-2 affects almost all laboratory species³. It makes vaccine development begin with animal injection trials before human trials. The primary endpoints include subgenomic (sg) RNA and viral genomic (g) RNA from the bronchoalveolar lavages and throat webs. For the covid-19 tests, the standard laboratory mice strains were considered resistant to the infection, which was overcome by using adapted viruses of mice to reflect human angiotensin-converting receptors by using different methods³. Notably, compared to experimental animal tests, human trials offer two advantages. First, unlike animal laboratory trials, human studies do not have Species differences that might affect the outcomes². Humans are subjected to various hazardous stressors before, during, or after trials, yielding outcomes closely resembling real-life experiences. Humans become more relevant in all circumstances because their outcome reflects the actual and expected vaccination findings².

Nevertheless, the general stages of vaccine development constitute authorization or approval. Before availing the vaccine to the public, the FDA assesses the outcomes of the clinical trials. Initially, they determine if the vaccines meet the set effectiveness standards and grant them Emergency Use Authorizations (EUAs)¹. The EUAs allow the vaccines to be distributed fast while observing the same level of safety. FDA also provides approval by following the built-in data and information given to the EUA. These processes include the preclinical and clinical data and data and reviewing the manufacturing processes to ensure that the vaccine meets safe manufacturing standards¹. Besides, as the vaccine is distributed, the state medical agencies provide several monitoring systems to enhance tracking. Hundreds of millions in the United States have received the covid-19 vaccine; they indicate no side effects under strict control and vaccine maintenance. However, some suggest minor and common side effects after the vaccination, such as swelling during the injection, pain, chills, fever, and headache. So, generally, the public indicates rare serious effects from covid-19 vaccinations ¹.

The post-trial access involves subjects’ access to the developed vaccines. In this part, they create a direct connection with these vaccine researches. Notably, the current covid-19 vaccines development involved intercontinental and multi-county approaches to recruiting individuals from different regions. It entailed community engagement, incorporating all stakeholders such as industries, investigators, sponsors, government, and trial subjects⁷. It involves observing ethical and human points of view. They attempt to meet the vaccines’ safety, efficacy, and tolerability. Even with the safety observations, the models of vaccine development can expose some participants to vulnerable health conditions.

The technological platforms of the vaccine development included nucleic acid (RNA and DNA), virus-like a particle, peptides, and viral vectors. First, the viral vector-based vaccination uses a reformed virus vector to yield a genetic code against the antigen¹. The viruses survive by invading the host cells and collapsing their protein-making component. These virus particles also have antigens—chemicals that can stimulate antibody responses. Virus vector vaccines work almost the same approach, except that their host cells receive code to assembly antigens¹. A viral vector serves as a delivery system, allowing it to enter the cell and insert the coding for the antigen of a different viral (the disease you’re attempting to protect against). The virus is harmless, and by instructing the cells to generate just antigens, the liver can build an immune reaction while avoiding sickness. They are produced by growing cells at the attached substrate but not the free-floating cells. The suspension cell lines are now impeded, enabling the viral vectors to emerge in large bioreactors¹. It also involves other steps and constitutes that make it less effective by increasing the contamination rate.

Secondly, the peptide vaccine technologies entail identifying, constructing, and selecting candidate epitope vaccine antigens accompanied by the chemical synthesis of antigenic peptides⁵. The peptide vaccines are mainly considered to induce broad-spectrum immune fighting strains of a specific pathogen by formulating several non-contiguous epitopes conserved between the pathogen’s strains⁵. Notably, various considerations are made when developing a peptide vaccine. They first begin by describing the immune-dominant domains that act as the inducing protective responders. On the other hand, some of the peptides are used to identify the epitopes that induce cytotoxic T cells⁵. Thus, they convey several advantages, including focusing on more immune reactions toward critical neutralizing epitopes. Besides, they are small, safe, and economical.

Additionally, the mRNA and DNA-based vaccine technologies reflect similar gene therapy in a specific system such as a plasmid, delivering targeted DNA into cells. It is later translated into proteins to induce the acceptor’s immune reactions to develop targeted T-cell and antibody feedbacks. In this model, the vaccine administration is different from gene therapy because it is safe for human subjects. Appraising the risk assessment of this technology relies on a theoretical framework with no direct evidence connecting it to the risk probability. These DNA vaccines can impede auto-immune systems or diseases and can be put in any part of the chromosomes.

On the other hand, virus-like particles are multi-protein structures that emulate the conformation of the target virus but without the viral genome. The approach yields top a safer and cheaper vaccine candidate. They lack the viral genetic components, thus un-harmful to the human body. According to (Nooraei et al.) Virus-like particles (VLPs) can elicit both cell-mediated immune responses and the antibodies responding by pathways different from those produced by the convection-inactivated viral vaccines⁶. VPLs categorized as subunit vaccines are later divided into non-envelop and envelop types. The development of the VLPs includes the spontaneous connection between the structural capsid proteins to develop the final structure. Although they are visually similar to the target viruses, they lack the entire virus genome. The structural and functional properties adopted in VPLs make the method attractive. Spontaneous polymerization of the several viral capsid proteins yields the VPLs with geometry evenness either in the form of rod-like, spherical, or icosahedral structures corresponding to the structures of the derived virus⁶. Their categorization, either with or without an envelope, provides an additional classification of their structure during their development. The enveloped VPLs have a matrix protein found immediately after in the host-derived lipid membrane from which the proteins are entrenched. For non-envelop VPLs, there are multi-capsid and single protein VPLs⁶. The single-capsid protein is found in the cell-free systems, and sometimes, it can be expressed in the prokaryotic and eukaryotic systems⁶. On the other hand, the multi-capsid production is assembled in different layers and made in heterogeneous hosts such as the bluetongue virus, infectious bursal disease virus, and rotavirus.

VPLs can be made using different expression systems comprising VPL assembly by polymerization due to the expression of virus protein components. Protein expression for VLP synthesis is extremely adaptable, allowing for substituting strain-specific amino acid sequences or introducing foreign peptides or proteins. Modifying this mechanism might make it easier to create recombinant chimeric VLPs with xenogeneic determinants, which would trigger an immune reaction alongside targets other than the parent virus. Virus-like particles can also guarantee self-antigens in an immunogenic setting, essential in covid-19 immune vaccination⁶. This form of alteration has been studied as a preventive treatment for various illnesses, including protection against other organisms’ infection, auto-immune inflammatory disease, and anticancer immunotherapy. Thus, the VPLs model of providing repetitive surface patterns sustains the immune and prevents the Covid-19 spread⁶. VLPs can be considered more effective than others of the three technologies. They can be used as preventive vaccines for showing foreign antigens on their surface to trigger the immune systems. In addition, it can also prevent other related infectious diseases apart from the subject infection. It is also a therapeutic vaccine presenting patients’ own antigens, which help them fight against metabolic, chronic, or different types of cancer. The surface of VLP can also be changed to meet desired specific tissues. Unfortunately, even with VLP-based vaccines’ success in preventing covid-19, there are still some complications in the area that require some time and research to overcome.

The ethical issues of the development of the covid-19 vaccine may change due to the spread of the infection. The public officers, heads of state, and researchers have to decide on the ethical mass production of effective vaccines on the limited date samples². The need to protect millions of people from the pandemic pushes the government into the great expectation of the pandemic. Thus, mRNA and DNA-based technologies are being used to curb the spread². The likely impacts of these technologies include the potential risks to type I interferon responses leading to auto-immune and inflammation conditions. Thus, this indicates a need for more observations and analysis of covid-19 vaccine technologies to yield effective and efficacy results.

Conclusion

Overall, the covid-19 pandemic, since its upsurge, has led to many health, social and economic impacts across the globe. Since its impacts were overwhelming, scientists had to develop its prevention and cure within the shortest time possible. This has led to the development of various vaccines; they undergo all the likely vaccine development stages; however, they would overlap to enhance their approval and consumption to the public. Consequently, such measures, at a point, fail to meet ethical standards of vaccine development. Thus, even with no side effects to the public consumption of the vaccines, it may correspond to low vaccine effectiveness and efficacy. On the other hand, the material appraises three likely vaccine development technologies, including virus-like particles, peptides, and viral vectors. Among the three, the article argues that the virus-like particles are the most effective because they mimic the target vaccine; however, they have no features of viral genomes. It ensures individuals have an antibody system to fight the virus.

References

1. Gavi.org. “What Are Viral Vector-Based Vaccines and How Could They Be Used Against COVID-19?”. Gavi.Org, 2022, https://www.gavi.org/vaccineswork/what-are-viral-vector-based-vaccines-and-how-could-they-be-used-against-covid-19.
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6. Nooraei, Saghi, et al. “Virus-like particles: Preparation, immunogenicity and their roles as nano vaccines and drug nanocarriers.” Journal of nanobiotechnology1 (2021): 1-27.
7. Wibawa, T. “COVID‐19 vaccine research and development: ethical issues.” Tropical Medicine & International Health1 (2021): 14-19.