Nucleic Acid Vaccines for COVID-19: A Paradigm Shift in the Vaccine Development Arena

Coronavirus disease, COVID-19, has touched every country globally except five countries (North Korea, Turkmenistan, Tonga, Tuvalu and Nauru). Vaccination is the most effective method to protect against infectious diseases. The objective is to ensure that everyone has access to a COVID-19 vaccine. The conventional vaccine development platforms are complex and time-consuming to obtain desired approved vaccine candidates through rigorous regulatory pathways. These safeguards guarantee that the optimized vaccine product is safe and efficacious for various demographic populations prior to it being approved for general use. Nucleic acid vaccines employ genetic material from a pathogen, such as a virus or bacteria, to induce an immune response against it. Based on the vaccination, the genetic material might be DNA or RNA; as such, it offers instructions for producing a specific pathogen protein that the immune system will perceive as foreign and mount an immune response. Nucleic acid vaccines for multiple antigens might be made in the same facility, lowering costs even more. Most traditional vaccine regimens do not allow for this. Herein, we demonstrate the recent understanding and advances in nucleic acid vaccines (DNA and mRNA based) against COVID-19, specifically those in human clinical trials.

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The Key Role of Nucleic Acid Vaccines for One Health

Viruses ◽

10.3390/v13020258 ◽

2021 ◽

Vol 13 (2) ◽

pp. 258

Author(s):

Anders Fomsgaard ◽

Margaret A. Liu

Keyword(s):

Nucleic Acid ◽

Real World ◽

Plasmid Dna ◽

One Health ◽

New Technologies ◽

Vaccine Development ◽

Emerging Diseases ◽

Nucleic Acid Vaccines ◽

Key Aspects

The ongoing SARS-CoV-2 pandemic has highlighted both the importance of One Health, i.e., the interactions and transmission of pathogens between animals and humans, and the potential power of gene-based vaccines, specifically nucleic acid vaccines. This review will highlight key aspects of the development of plasmid DNA Nucleic Acid (NA) vaccines, which have been licensed for several veterinary uses, and tested for a number of human diseases, and will explain how an understanding of their immunological and real-world attributes are important for their efficacy, and how they helped pave the way for mRNA vaccines. The review highlights how combining efforts for vaccine development for both animals and humans is crucial for advancing new technologies and for combatting emerging diseases.

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Host protein glycosylation in nucleic acid vaccines as a potential hurdle in vaccine design for nonviral pathogens

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1916131117 ◽

2020 ◽

Vol 117 (3) ◽

pp. 1280-1282 ◽

Cited By ~ 1

Author(s):

Ahmet Ozdilek ◽

Amy V. Paschall ◽

Michelle Dookwah ◽

Michael Tiemeyer ◽

Fikri Y. Avci

Keyword(s):

Immune Response ◽

Nucleic Acid ◽

Mammalian Cells ◽

Secretory Pathway ◽

Surface Protein ◽

Amino Acid Sequences ◽

Protein Glycosylation ◽

Host Protein ◽

Host Cells ◽

Nucleic Acid Vaccines

Nucleic acid vaccines introduce the genetic materials encoding antigenic proteins into host cells. If these proteins are directed into the secretory pathway with a signal/leader sequence, they will be exposed to the host’s glycosylation machinery, and, if their amino acid sequences contain consensus sequons for N-linked glycosylation, they may become glycosylated. The presence of host glycans on the proteins of microbial origin may prevent a strong protective immune response either through hindering access to key epitopes by lymphocytes or through altering immune responses by binding to immunoregulatory glycan-binding receptors on immune cells. Ag85A expressed by Mycobacterium tuberculosis (Mtb) is a bacterial surface protein that is commonly used in nucleic acid vaccines in multiple clinical trials. Here we show that, when Ag85A is expressed in mammalian cells, it is glycosylated, does not induce a strong humoral immune response in mice, and does not activate Ag85A-specific lymphocytes as highly as Ag85A natively expressed by the bacterium. Our study indicates that host glycosylation of the vaccine target can impede its antigenicity and immunogenicity. Glycosylation of the antigenic protein targets therefore must be carefully evaluated in designing nucleic acid vaccines.

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Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy

Current Issues in Molecular Biology ◽

10.3390/cimb43010005 ◽

2021 ◽

Vol 43 (1) ◽

pp. 52-64

Author(s):

Mohammad Kayesh ◽

Md Hashem ◽

Kyoko Tsukiyama-Kohara

Keyword(s):

Immune Response ◽

Viral Infections ◽

Vaccine Development ◽

Effective Vaccine ◽

Therapeutic Tool ◽

Proper Understanding ◽

In Captivity ◽

In The Wild ◽

Koala Retrovirus ◽

Made In

Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for the host’s survival, as well as for the development of therapeutic and prophylactic interventions. A vaccine is an important protective as well as being a therapeutic tool against infectious disease, and several studies have shown promise for the development of an effective vaccine against KoRV. Moreover, CRISPR/Cas9-based genome editing has opened a new window for gene therapy, and it appears to be a potential therapeutic tool in many viral infections, which could also be investigated for the treatment of KoRV infection. Here, we discuss the recent advances made in the understanding of the immune response in KoRV infection, as well as the progress towards vaccine development against KoRV infection in koalas.

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Novel 2019 coronavirus: Genome structure, clinical trials, and outstanding questions

Experimental Biology and Medicine ◽

10.1177/1535370220920540 ◽

2020 ◽

Vol 245 (11) ◽

pp. 964-969 ◽

Cited By ~ 4

Author(s):

Manasi P Jogalekar ◽

Anurag Veerabathini ◽

Prakash Gangadaran

Keyword(s):

Clinical Trials ◽

Vaccine Development ◽

Genome Structure ◽

Genetic Material ◽

Effective Vaccine ◽

The Novel ◽

Causative Agents ◽

Novel Coronavirus ◽

Spreading Potential ◽

Conventional Vaccine

Novel 2019 coronavirus has created havoc across the globe since its emergence in December 2019 in Wuhan, China, and fast spreading potential. While we were able to identify the causative agent within a few days of the disease outbreak, several questions still remain unanswered. In this review, we discuss the extent of virus spread, current statistics, SARS-CoV-2 genome organization, comparison between the novel coronavirus and causative agents involved in previous outbreaks, ongoing clinical trials and myths associated with the virus. Lastly, we provide insights into the future perspectives which could prove useful for the scientific community as they work on finding the cure against the disease. Impact statement Early availability of the sequence, the genetic material of SARS-CoV-2 (the virus that causes COVID-19), has prompted efforts towards identifying a safe and effective vaccine in the current public health emergency. To that end, understanding the pathophysiology of disease is crucial for scientists around the world. Since conventional vaccine development and manufacturing may take several years, it is important to think about alternative strategies that we could use to mitigate imminent catastrophe. We hope that this article will open up new avenues and provide insights that could potentially save hundreds of lives affected by COVID-19.

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HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

Protein and Peptide Letters ◽

10.2174/0929866528999201231213610 ◽

2020 ◽

Vol 28 ◽

Author(s):

Alireza Milani ◽

Kazem Baesi ◽

Elnaz Agi ◽

Ghazal Marouf ◽

Maryam Ahmadi ◽

...

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Treated Group ◽

Vaccine Antigen ◽

Accessory Proteins ◽

Serological Method ◽

Th2 Immune Response ◽

Untreated Individuals ◽

Immunogenic Properties ◽

Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

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Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽

10.3390/pharmaceutics13020140 ◽

2021 ◽

Vol 13 (2) ◽

pp. 140

Author(s):

Abdellatif Bouazzaoui ◽

Ahmed A. H. Abdellatif ◽

Faisal A. Al-Allaf ◽

Neda M. Bogari ◽

Saied Al-Dehlawi ◽

...

Keyword(s):

Viral Vectors ◽

Protein Production ◽

Vaccine Development ◽

Effective Vaccine ◽

The Novel ◽

Research Teams ◽

Advantages And Disadvantages ◽

Rapid Spread ◽

New Generation ◽

Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

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The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

Animals ◽

10.3390/ani11020380 ◽

2021 ◽

Vol 11 (2) ◽

pp. 380

Author(s):

Bonnie L Quigley ◽

Peter Timms

Keyword(s):

Immune Response ◽

Chlamydial Infection ◽

Vaccine Development ◽

Interleukin 17 ◽

Phascolarctos Cinereus ◽

Post Vaccination ◽

Research Systems ◽

Cytokine Levels ◽

Nucleic Acid Assay ◽

Immunological Research

Chlamydia is a significant pathogen for many species, including the much-loved Australian marsupial, the koala (Phascolarctos cinereus). To combat this situation, focused research has gone into the development and refinement of a chlamydial vaccine for koalas. The foundation of this process has involved characterising the immune response of koalas to both natural chlamydial infection as well as vaccination. From parallels in human and mouse research, it is well-established that an effective anti-chlamydial response will involve a balance of cell-mediated Th1 responses involving interferon-gamma (IFN-γ), humoral Th2 responses involving systemic IgG and mucosal IgA, and inflammatory Th17 responses involving interleukin 17 (IL-17) and neutrophils. Characterisation of koalas with chlamydial disease has shown increased expression within all three of these major immunological pathways and monitoring of koalas’ post-vaccination has detected further enhancements to these key pathways. These findings offer optimism that a chlamydial vaccine for wider distribution to koalas is not far off. Recent advances in marsupial genetic knowledge and general nucleic acid assay technology have moved koala immunological research a step closer to other mammalian research systems. However, koala-specific reagents to directly assay cytokine levels and cell-surface markers are still needed to progress our understanding of koala immunology.

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Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz518 ◽

2019 ◽

Vol 222 (4) ◽

pp. 572-582 ◽

Cited By ~ 6

Author(s):

Louis Fries ◽

Iksung Cho ◽

Verena Krähling ◽

Sarah K Fehling ◽

Thomas Strecker ◽

...

Keyword(s):

Public Health ◽

Immune Response ◽

Ebola Virus ◽

Vaccine Development ◽

Phase 1 ◽

Healthy Adults ◽

Wild Type ◽

Dose Ranging ◽

Further Development ◽

Human Vaccine

Abstract Background Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development. Methods A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year postdosing. Results All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP immunoglobulin G titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type Zaire EBOV (ZEBOV) or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year. Conclusions Ebola virus GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted.

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