COVID-19 is still a global pandemic. Around the world, as of 5:40pm CEST, 26 April 2023, there have been 764,474,387 cumulative confirmed cases of COVID-19, including 6,915,655 deaths, reported to the World Health Organization. As of 24 April 2023, a total of 13,325,228,015 vaccine doses have been administered. The adoption of vaccines worldwide continues to increase, yet periodic spikes and surges in infection rates continue to occur with new SARS-CoV-2 variants, such as that observed in Australia in Jan 2022. Vaccine booster doses provide effective protection against developing severe disease and hospitalization, but vaccine adoption and distribution face ongoing challenges in low- and middle-income (LMIC) countries (1). The development of intranasal vaccines could help alleviate some of the challenges in these areas. Therapeutic interventions for those already infected are in development, with one (Paxlovid) currently available under emergency use authorization (EUA) in the US.
Cumulative COVID-19 statistics by country: WHO COVID-19 Dashboard. Geneva: World Health Organization, 2020. Available online: https://covid19.who.int/ (last cited: April 28, 2023).
COVID-19 cases are now being identified primarily among unvaccinated individuals, according to data from the US Centers for Disease Control and Prevention (CDC). However, there has been increasing concern about so-called breakthrough infections among fully vaccinated individuals, particularly after the emergence of the SARS-CoV-2 Delta variant.
What is a breakthrough infection? The CDC defines it as “the infection of a fully vaccinated person.” The key finding remains that people with breakthrough infections are still far less likely to experience severe COVID-19 symptoms, in contrast with unvaccinated people; hence the importance of vaccination.
Oral vaccines are a great strategy and are especially beneficial in areas with poor sanitation. This form of vaccine distribution could help control the acute diarrheal disease caused by Vibrio cholera. There are an estimated 1.3 to 4 million cases and 21,000 to 143,000 deaths from cholera each year. A recent study from The Lancet Microbe finds new hope in a rice-based cholera vaccine that will fight against the diarrheal toxin without severe adverse events.
The global war against the coronavirus that causes COVID-19 rages on, spearheaded by efforts to develop effective and safe vaccines. At the time of writing, over 100 COVID-19 vaccine clinical trials were listed in the clinicaltrials.gov database. Recent attention has focused on mRNA vaccines developed by Pfizer/BioNTech and Moderna. If licensed, they would become the first mRNA vaccines for human use.
Multiple battles are being fought in the war against the SARS-CoV-2 coronavirus that causes COVID-19. Currently, there are nearly 5,000 clinical trials listed in the World Health Organization (WHO) database, either underway or in the recruiting stage, for vaccines and antiviral drugs. The Moderna mRNA vaccine and Janssen vaccine have received emergency use authorization (EUA) from the Food and Drug Administration (FDA); the Pfizer-BioNTech Vaccine (marketed as Comiraty) received FDA approval in August 2021.
Both the Moderna vaccine and Comiraty are mRNA-based, as opposed to most conventional vaccines against established diseases that are protein-based. Typically, the key ingredient in viral vaccines is either part of an inactivated virus, or one or more expressed proteins (antigens) that are a part of the virus. These protein antigens are responsible for eliciting an immune response that will fight future infection by the actual virus. Another approach is to use a replication-deficient viral vector (such as adenovirus) to deliver the gene encoding the antigen into human cells. This method was used for the coronavirus vaccine developed by Oxford University in collaboration with AstraZeneca; phase 3 interim data were announced on the heels of the Pfizer/BioNTech and Moderna announcements. All three vaccines target the SARS-CoV-2 spike protein, because it is the key that unlocks a path of entry into the host cell.
Developing a vaccine that is safe, effective, easily manufactured and distributed is a daunting task. Yet, that is exactly what is needed in response to the COVID-19 pandemic.
Vaccine development, safety and efficacy testing take time. The mumps vaccine is thought to be the quickest infectious disease vaccine ever produced, and its development required four years from sample collection to licensing (2). However, there are many reasons to anticipate quicker development for a COVID-19 vaccine: Researchers are collaborating in unprecedented ways, and most COVID-19 scientific publications are free for all to access and often available as preprints. As of August 11, 2020, researchers around the globe have more than 165 vaccine candidates in development, 30 of which are in some phase of human clinical trials (1). The range of vaccine formulations available to scientists has expanded to include RNA and DNA vaccines, replication-defective adenovirus vaccines, inactivated or killed vaccines and subunit protein vaccines. Equally important is that vaccine developers and researchers have greater access to powerful molecular biology tools like bioluminescent reporters that enable quicker testing and development.
Transcription is the production of RNA from a DNA sequence. It’s a necessary life process in most cells. Transcription performed in vitro is also a valuable technique for research applications—from gene expression studies to the development of RNA virus vaccines.
During transcription, the DNA sequence is read by RNA polymerase to produce a complimentary, antiparallel RNA strand. This RNA strand is called a primary transcript, often referred to as an RNA transcript. In vitro transcription is a convenient method for generating RNA in a controlled environment outside of a cell.
In vitro transcription offers flexibility when choosing a DNA template, with a few requirements. The template must be purified, linear, and include a double stranded promoter region. Acceptable template types are plasmids or cloning vectors, PCR products, synthetic oligos (oligonucleotides), and cDNA (complimentary DNA).
In vitro transcription is used for production of large amounts of RNA transcripts for use in many applications including gene expression studies, RNA interference studies (RNAi), generation of guide RNA (gRNA) for use in CRISPR, creation of RNA standards for quantification of results in reverse-transcription quantitative PCR (RT-qPCR), studies of RNA structure and function, labeling of RNA probes for blotting and hybridization or for RNA:protein interaction studies, and preparation of specific cDNA libraries, just to name a few!
In vitro transcription can also be applied in general virology to study the effects of an RNA virus on a cell or an organism, and in development and production of RNA therapeutics and RNA virus vaccines. The large quantity of viral RNA produced through in vitro transcription can be used as inoculation material for viral infection studies. Viral mRNA transcripts, typically coding for a disease-specific antigen, can be quickly created through in vitro transcription, and used in the production of vaccines and therapeutics.
As the SARS-CoV-2 coronavirus continues to spread throughout the world, the race is on to produce antivirals and vaccines to treat and prevent COVID-19. One potential treatment is the use of human monoclonal antibodies, which are antibodies engineered to target and block specific antigens. A recent study by Wang, C. and colleagues published in Nature Communications showed that human monoclonal antibodies can be used to block SARS-CoV-2 from infecting cells.
A paper published last week in Science Translational Medicine describes promising results from a phase 1 clinical trial of a new anti-tuberculosis vaccine. The vaccine, composed of a human Adenoviral vector expressing a Mycobacterium tuberculosis antigen, generated an immune response in people with and without previous exposure to the current anti-tuberculosis (BCG) vaccine.
Mycobacterium tuberculosis, discovered by Robert Koch in 1882, is the organism that causes tuberculosis—commonly known as TB. After introduction of the BCG (Bacille Calmette-Guérin ) vaccine in 1919 and antibiotic treatment in the 1950s, the hope was that TB would be finally consigned to history—that Mycobacteruim tuberculosis would be a name only associated with the pre-antibiotic era and would not be a part of the 21st century world. However, over the last 30 years the emergence of multi-drug resistance and the worldwide HIV epidemic have led to the re-emergence of TB to the point where the following statements are true: Continue reading “TB Vaccine News”
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