According to real-time data from Johns Hopkins University, as of January 25, the total number of confirmed cases of COVID-19 around the world was 99.269 million, with 25.128 million in the United States, India ranking second with 10.668 million, accounting for 25.3% and 10.7% individually of all. There are more than 1 million cases in 16 countries, which are Brazil, Russia, Britain, France, Spain, Italy, Turkey, Germany, Colombia, Argentina, Mexico, Poland, South Africa, Iran, Ukraine, and Peru. The number of confirmed cases in China (including Hong Kong and Macau), which reported the epidemic first, continues to decline, and now ranks 82.

The total number of deaths worldwide is 2.131 million.

In mid-December 2020, the FDA successively approved emergency marketing permits for the COVID-19 vaccines of Pfizer and Modena, which were fully put into production, distributed to all parts of the United States in proportion to the population, and given to people for free in accordance with pre-established priorities.

The pharmaceutical giant Merck announced that it will stop the development of V590 and V591, the two COVID-19 vaccine candidates, and continue to develop two research-based therapeutic vaccine candidates.

Merck is a pioneer in the vaccine R&D. Since its establishment 125 years ago, Merck has been providing medicines and vaccines for tricky diseases to the whole world, making contributions to the prevention and treatment of diseases that threaten humans and animals, including cancer, HIV, Ebola, and emerging animal diseases.

For COVID-19 vaccine development, Merck tried two viral vector vaccines, measles virus vector and vesicular stomatitis virus vector. However, the Phase 1 clinical study revealed that although V590 and V591 are well tolerated, the immune effects were far from satisfactory, and the level of antibodies produced was even lower than that of recovered patients.

In contrast, the vaccine jointly developed by Pfizer and BioNTech and the vaccine developed by Moderna could stimulate antibodies several times that of recovered patients. The adenovirus vector vaccine jointly developed by AstraZeneca and Oxford could produce antibodies comparable to those of recovered patients.

Therefore, Merck had to terminate the development of these two candidate vaccines. Meanwhile, Merck announced that it will apply the research strategy and production capacity to the promotion of two therapeutic SARS-CoV-2 vaccine candidate, MK-4482 and MK-7110, and expand the scale of production.

MK-7110 (previously known as CD24Fc) is the first investigative recombinant fusion protein of its kind, which mainly regulates the inflammatory response caused by SARS-CoV-2 by targeting checkpoints of new immune pathways. The phase 3 study interim results showed that the risk of death or respiratory failure in hospitalized patients with moderate to severe symptoms was reduced by more than 50%.

Molnupiravir (MK-4482), an oral antiviral drug developed jointly with Ridgeback Bio, is currently undergoing phase 2/3 clinical trial in hospitals and outpatients.

Strategies to build a safe and effective COVID-19 vaccine mainly involve antigen (https://www.creative-biolabs.com/vaccine/category-antigens-1.htm), vector, and vaccination plan.

Antigen
The viral structures with affinity include S protein, N protein, matrix (M) protein, and envelope protein (E). For SARS-CoV-2, it was proved that only antibodies targeting the S protein can neutralize the virus and prevent infection.

Vector
Vaccine vectors are generally divided into six categories, which are live attenuated viral vectors, recombinant viral vectors, inactivated viral vectors, protein subunit vectors, virus-like particles (VLPs), and DNA or RNA.

Vaccination route and plan
The best opportunity for SARS-CoV-2 control and elimination is in the asymptomatic or early stage of infection (2-14 days), which may require all immune components to be in the mucosa before the virus enters. Neither live attenuated vaccines, protein subunits vaccines, or nucleic acid vaccines can be injected through the respiratory mucosal route. In contrast, recombinant viral vector vaccines are safe and efficient for the vaccination of respiratory mucosa.

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