Searching for a COVID-19 Vaccine

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The following article was written by Stefan Malmoli, editor of AccessScience, has been republished in full from AccessScience.com

In response to the COVID-19 (coronavirus disease 2019) pandemic—which has dramatically affected the entire world, causing high morbidity, mortality, and massive social and economic disruption—and in addition to finding efficacious treatments for individuals severely affected by COVID-19, the global scientific community is focused on developing a safe and effective vaccine (or a number of different vaccines) to halt the pathogenic effects of the specific coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—that causes COVID-19 in humans. Some researchers are confident that the swift discovery of a successful vaccine is feasible, possibly as early as late 2020 or early 2021. The potentially rapid development of a COVID-19 vaccine would reduce the degree and risk of infection, thereby decreasing transmission rates and ultimately controlling and ending the pandemic. However, other researchers are cautious about such an optimistic timeline because histories of past vaccine discoveries indicate that the process of creating a safe and effective vaccine is arduous, encompassing many years of research and clinical trials. Moreover, certain diseases have eluded efforts by scientists to find an effective vaccine. For example, there is as yet no vaccine to combat human immunodeficiency virus [HIV, the retrovirus that causes acquired immune deficiency syndrome (AIDS)], despite decades of research to develop such a vaccine. See also: Acquired immune deficiency syndrome (AIDS)CoronavirusEpidemicHuman immunodeficiency virus (HIV)ImmunologyInfectionNovel coronavirus is declared a global pandemicPathogenVaccination

Four coronaviruses, colorized predominantly light red/pink, with each having a thin yellow circular border and bluish spur-shaped proteins protruding from the surface of each virus particle, on a black background
Colorized transmission electron microscope image of SARS-CoV-2 coronaviruses. Spike (S) proteins can be seen on the outer edges of the virus particles. (Credit: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases)

The goal of vaccination is to immunize individuals against an infectious microorganism (or its components), thereby protecting the host against subsequent challenge by the infectious agent. Specifically, vaccines trigger an immune response against a particle or cell contained within the vaccine, which then leads to an "immunological memory" within the body and long-term protection against the target pathogen. The process of vaccine development is conducted incrementally, utilizing steps or stages involving potential vaccine identification, preclinical work, and, typically, three phases of clinical trials. If the vaccine is deemed successful, regulatory and governmental review and approval are mandated. The final stage of manufacturing astronomically large numbers of vaccine doses also requires a great deal of quality-control testing, so the total elapsed time from start to finish of vaccine development is never brief. For example, the shortest amount of time-to-market occurred in the case of the mumps vaccine, which required four years (in the 1960s) for the vaccine to be developed, approved, and marketed for use. See also: BiologicalsClinical immunologyImmunityMumpsProduction lead timeQuality control

Numerous pharmaceutical companies, scientific institutions, and government agencies in the United States, China, and multiple European countries began research efforts in early 2020 to identify COVID-19 vaccine prospects. Preliminary evidence indicates that individuals infected with SARS-CoV-2 produce antibodies, which are proteins in blood that neutralize viruses. Moreover, because scientists in China determined the genomic sequence of SARS-CoV-2 in January 2020, certain vaccine efforts are concentrating on genomic methodologies, particularly those involving DNA or messenger RNA (mRNA). For example, a promising mRNA vaccine candidate (mRNA-1273) has been developed by Moderna in Cambridge, Massachusetts. The first clinical batch of mRNA-1273 was completed in early February 2020, and early-phase clinical trials in humans were fast-tracked in May 2020. Researchers have since detected antibody production in the initial study group that received the potential vaccine, and levels of those neutralizing antibodies were high enough to confer immunity against COVID-19. Importantly, no lingering side effects were noted. However, no mRNA vaccines have thus far been approved for use in humans. See also: AntibodyCellular immunologyDeoxyribonucleic acid (DNA)DNA vaccinationGenetic mappingNeutralizing antibodyRibonucleic acid (RNA)

Other research efforts are targeting the molecular structure of SARS-CoV-2 in attempts to pinpoint a vaccine. For example, spike (S) proteins, which protrude from the coronavirus's surface, are responsible for attaching the virus to a receptor present on the surface of a host cell. Most importantly, S proteins mediate fusion of the coronavirus with host cell membranes, allowing entry of the virus into the host cell. As such, S proteins are the main targets for antibodies produced by the body as an immune defense against the coronavirus. Thus, if binding of S proteins to host cell receptors could be blocked, as would be the case with an effective vaccine, the virus would not be able to enter the host cell. See also: Cell membraneProteinVirus

Ad5-nCoV, an engineered adenoviral-vector vaccine that contains adenovirus type 5 (a common cold virus), is a promising vaccine candidate that impedes S protein binding. When the vaccine is deployed into a host and recognized by the host’s immune system, neutralizing antibodies against the S proteins of SARS-CoV-2 are produced. Ad5-nCoV was developed by CanSino Biologics in China, and phase-II trials have been ongoing since April 2020. So far, the results of this vaccine have been positive in 108 human test subjects, who have been assessed with regard to both the safety of the vaccine and its ability to generate a successful immune response. See also: Adenoviridae

Another prototype vaccine, Ad26, which is a chemically disabled version of an adenovirus that has been engineered to contain a gene for the S proteins of SARS-CoV-2, has tested successfully in eight rhesus monkeys. The Ad26 vaccine was created by researchers at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts, in March 2020, with positive results being reported in late May 2020. Deployment of this vaccine caused the monkeys to produce neutralizing antibodies against SARS-CoV-2. However, monkeys typically fail to develop the most severe symptoms that SARS-CoV-2 causes in humans, so it is unknown whether humans would develop similar immunity to the coronavirus as the monkeys did in response to the vaccine. Still, the ability of a vaccine to work efficaciously in an animal model is a hopeful sign that such a vaccine may work in humans. See also: Animal testing

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