Vaccine Development Strategies and the Current Status of COVID-19 Vaccines
Debmalya Barh, Kenneth Lundstrom in COVID-19, 2022
Vaccines designed to combat SARS-CoV-2 can be classified based on their function and the life cycle of the virus in infected human cells. SARS-CoV-2 vaccines are generally based on inactivated or attenuated viruses, protein subunits and peptides, viral vectors and nucleic acids [5, 6]. Nucleic acid–based vaccines, DNA and RNA vaccines, contain sequences that can encode the virus spike protein, which eventually induce immune responses. Adenovirus vector-based vaccines, because of the presence of viral proteins on their surface, can elicit immune responses, such as stimulation of toll-like receptors (TLR). Also, antigens, such as protein subunit vaccines, can provoke cell-dependent immune responses [7]. However, some vaccines are not able to produce adequate immune responses. Therefore, some adjuvants are used to enhance immune responses or the resulted responses to specific and desired pathways.
Taming the Enemy
Norman Begg in The Remarkable Story of Vaccines, 2023
The second type of genetic vaccine is based on mRNA, the messenger of DNA. When injected, mRNA vaccines directly instruct the body to make antigen. Unlike DNA, RNA is unstable and gets broken down by your body soon after being injected. To prevent this from happening too quickly, it needs to be protected with something (often a lipid, which is a type of fat) before being injected. Even with this protective coat, the RNA only lasts a few hours, so it’s a race against time to make the antigen. Some types of mRNA vaccines use a trick of modifying the RNA so that it is able to multiply inside the cell, known as self-amplifying messenger RNA or SAM for short. Like DNA vaccines, mRNA vaccines produce a broad range of immune responses but are even easier to manufacture. Two of the earliest approved COVID-19 vaccines, from Pfizer/BioNTech and Moderna, are mRNA-based.
The Challenge of Parasite Control
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
Several newer vaccine types have been developed, some of which are acellular vaccines in that they do not include whole organisms. An example is the subunit vaccine, in which the vaccine consists of particular immunostimulatory antigens only. The hepatitis B vaccine, for instance, is composed only of viral surface proteins. Our understanding of the stimulatory role of T cells in a humoral response has resulted in the development of conjugate vaccines (Figure 9.28). These vaccines rely on a combination of antigens that stimulate both B and T cells. The Haemophilus influenzae vaccine, for instance, combines polysaccharides found in the bacterial capsule with peptides recognized by antigen-specific T cells. The result is a much stronger antibody response then could be elicited with the polysaccharides alone. And most recently, used clinically only since late 2020, are the mRNA vaccines used against the SARS-CoV-2 virus that causes Covid-19. These vaccines consist of viral mRNA that encodes an antigenic viral peptide. The RNA is surrounded by a lipid-based vesicle, which fuses with host cells, allowing the RNA to enter these cells. The viral mRNA is subsequently translated by host translation machinery and the resulting viral peptide is released from the cell where it stimulates an immune response. See the web callout associated with this section to learn about other vaccine types, including those based on nucleic acid.
An update on COVID-19 pandemic: the epidemiology, pathogenesis, prevention and treatment strategies
Published in Expert Review of Anti-infective Therapy, 2021
Hin Fung Tsang, Lawrence Wing Chi Chan, William Chi Shing Cho, Allen Chi Shing Yu, Aldrin Kay Yuen Yim, Amanda Kit Ching Chan, Lawrence Po Wah Ng, Yin Kwan Evelyn Wong, Xiao Meng Pei, Marco Jing Woei Li, Sze-Chuen Cesar Wong
RNA vaccines involve the introduction of RNA sequence encoding for the antigen to induce adaptive immune response [79]. RNA does not integrate into host genome. The risk of insertional mutagenesis and anti-vector immunity can be avoided [79]. However, introduction of RNA strand in the vaccine may elicit unintended immune response which raises safety concern of the vaccine. Delivering RNA vaccine effectively to the target tissue is challenging because RNA vaccines are temperature sensitive and are broken down easily [79]. An mRNA-based vaccine, mRNA-1273, co-developed Moderna and the Vaccine Research Center at the National Institutes of Health that expresses has entered phase III clinical trial (ClinicalTrials.gov: NCT04470427). It targets antigen in vivo and elicits antiviral response toward the spike proteins of SARS-CoV-2 after intramuscular injection to human bodies.
The race for a COVID-19 vaccine: where are we up to?
Published in Expert Review of Vaccines, 2022
Md Kamal Hossain, Majid Hassanzadeganroudsari, Jack Feehan, Vasso Apostolopoulos
The RNA vaccines are similar to DNA vaccines, including mRNA coded for disease-causing microorganism antigens (such as the SARS-CoV-2 spike protein. Similar to DNA vaccines, upon administration, the patient’s cells translate the RNA, producing the antigen by reading the genetic code on mRNA. The antigen produced is then secreted and is presented to the body’s immune system to produce antibodies. This platform has been explored for a number of infectious disease vaccines, including SARS and MERS [73]. Currently, 42 candidates from this platform are under investigation for the COVID-19 vaccine. RNA vaccines can be developed quickly in laboratory settings and could save considerable time. However, this platform is also associated with some challenges because the RNA vaccines may lead to undesired side effects, and precise delivery of the RNA into the cells is difficult due to the rapid breakdown of free RNA.
Microfluidic production of mRNA-loaded lipid nanoparticles for vaccine applications
Published in Expert Opinion on Drug Delivery, 2022
Carolina Lopes, Joana Cristóvão, Vânia Silvério, Paulo Roque Lino, Pedro Fonte
NA-based vaccines include viral vectors, plasmid DNA and mRNA [8,9]. These therapeutics promote vaccine development against a wide range of pathogens, as they support the delivery of any antigen of choice, regardless of whether it is derived from bacteria, parasite, or virus, and their immune responses are focused only on the antigens of interest [9]. The mRNA vaccines have shown significant interest for the treatment against infectious diseases and several types of cancer. The use of mRNA-based vaccines has several benefits over conventional live attenuated and DNA-based vaccines. Because live attenuated vaccines show higher potency, there is an associated risk of reverting to a pathogenic form and cause infection. In comparison to DNA-based vaccines, mRNA therapeutics are easier to deliver as RNA only needs to be delivered into the cytoplasm of the host cell to be translated into protein. Also, mRNA therapeutics are safer since RNA cannot integrate his genome in the host cell. RNA exhibits shorter half-life, hence only a low level of expression can be achieved in vivo, resulting in a more controllable therapy in case of adverse effects. On top of all the above, mRNA vaccines allow rapid and easy development. Indeed, production of mRNA by a cell-free environment by in vitro transcription of a DNA template that contains the mRNA sequence avoids the use of microorganisms or cultured cells, allowing simple downstream purification and very rapid and cost-effective manufacturing [10].