The Puerto Rico National Guard began to vaccinate residents and personnel of the island's aegis against COVID-19 on January 27. The PRNG expects to complete the first and second doses by the middle of March. (Photo by Army National Guard Staff Sgt. Alexis Velez.)
“These asymptomatic people may mount an immune response to infection before experiencing symptoms, or they may tolerate infection without symptoms,” explained Ryan. “While it is not entirely clear why some people do not develop symptoms and some people develop only mild symptoms, we know some factors that increase risk of serious infection.”
For example, she said older age is an important risk factor for serious COVID-19 infection. “There is no absolute age when risk increases, but 80% of COVID-19 deaths have occurred in people older than age 65.”
Many underlying medical conditions can increase the risk of serious COVID-19, including but not limited to chronic lung, heart, and kidney disease; diabetes; cancer; and immune-compromising conditions, such as obesity and pregnancy. Smoking can also increase the risk for illness, she said.
Over the last weeks of 2020 and first weeks of 2021, new variants of SARS-CoV-2 have been identified across the globe, alarming the public and raising concerns about the efficacy of the vaccines.
“Coronaviruses are part of a large family of viruses that are capable of genetically evolving or changing over time,” explained Ryan. “In fact, SARS-CoV-2 likely arose from a major genetic change in a coronavirus that was first identified in 2019.”
According to Cowden, “genetic substitutions in the virus genome will lead to the emergence of new strains as SARS-CoV-2 continues to circulate in the human population throughout the world.” Some of these new strains, or mutations, may lead to increased or decreased “fitness” of the virus, that is, “the changes in how easily it transmits or in virulence — how sick it makes people.
However, although some of these variants appear to be easily transmitted, they cause the same spectrum of symptoms, Ryan explained. “Spike-protein-based immune responses seem to be similar in new variants, which means current vaccines should be effective against these variants.”
Nonetheless, she said, scientists are examining the evolution of virus variants very carefully. Recent news reports from the United Kingdom say the new variant they identified among their population may not only be more contagious but could be more deadly as well.
How vaccines work
Pharmaceutical companies, universities, and government organizations around the world have been working against and around the clock since the beginning of the COVID-19 pandemic to develop a safe and effective vaccine to counter the rates of contagion. Pfizer-BioNTech and Moderna received the FDA’s emergency use authorization in the United States in mid-December 2020 for people ages 16 and older and 18 and older, respectively, but other promising candidates are in development by additional professional teams, including Janssen, AstraZeneca, and Novavax.
“The different vaccine candidates are all targeting the SARS-CoV-2 spike protein,” said Cowden. They work by presenting an antigen — a substance that the body does not recognize — to the body, she said.
The experts explained that antigens are introduced as a small piece of coding material, called messenger RNA (mRNA), into a few immune cells. It is encased in a lipid coat that allows it to enter only the outer part of the cells. It does not integrate into the person’s DNA or replicate, and it breaks down quickly, so it’s only present in the cell briefly.
“That mRNA then tells the cells to express ‘spike protein,’ resulting in the immune system making antibodies to destroy the spike protein,” said Ryan, adding that mRNA vaccines must be handled very carefully and often maintained at very cold temperatures to work properly.
Vaccines use different platforms to introduce the spike protein to the body to elicit the immune system’s response of blocking or killing the virus if a person becomes infected after vaccination, added Cowden. “Those antibodies then continue to be made by the body and can bind and/or neutralize the virus if an individual becomes infected after vaccination.”
Said Ryan: “The immune system also develops memory immune cells, so that any newly introduced spike protein would also be destroyed. Spike protein is similar to a protein on the coat of coronaviruses, so an immune response to spike protein can equate to immunity from coronavirus (SARS-CoV-2).”
Pfizer partnered with BioNTech to develop an mRNA vaccine that is administered in two injections given at least 21 days apart. Moderna developed a similar mRNA vaccine that also requires administration as two injections given at least 28 days apart. The mRNA technology in these does not include any virus.
Janssen, a subsidiary of Johnson & Johnson, developed a viral-vector vaccine to be administered in one injection. And AstraZeneca, in partnership with the University of Oxford, also developed a viral-vector vaccine that is to be administered in two injections at least 28 days apart. Both pharmaceuticals are likely to submit their products to FDA for emergency use authorization in the coming weeks.
“The Janssen and AstraZeneca/Oxford vaccines are both replication-deficient adenovirus-vectored vaccines,” said Cowden.
This means they use a different virus, such as measles or adenovirus, which is genetically engineered so that it can produce coronavirus proteins in the body and trigger the immune system to make antibodies against those proteins.
“After spike protein is expressed, the immune response is similar to that of mRNA vaccines: The immune system makes antibodies and memory immune cells that target spike protein. This response equates to immunity from SARS-CoV-2,” said Ryan.
The viruses used in viral-vector vaccines are weakened or inactivated, so they cannot cause disease or harm humans, said the experts. Viral-vector vaccines are also relatively fragile and must be maintained at temperatures that allow them to remain intact to work optimally.
Novavax developed an adjuvanted protein subunit vaccine to be administered in two injections at least 21 days apart. The experts explained this type of vaccine usually works by introducing a component of the virus — the antigen — into the body along with an adjuvant, a molecule composed of a cholesterol-like substance that stimulates the immune system, prompting the immune system to make antibodies against the protein antigen, resulting in immunity from the SARS-CoV-2 virus that causes COVID-19.
“Vaccines that use adjuvanted protein subunits introduce the spike protein directly,” said Ryan.
Unlike the others, this type of vaccine remains stable in refrigerated temperatures. When data from ongoing clinical trials is complete, Novavax will likely submit an application to FDA for emergency use authorization.
Why must some vaccines be kept in such cold temperatures?
Each vaccine is made differently. And each company is in different stages of testing the stability of its vaccine at different temperatures over time. However, the storage temperature requirements of each depend on the stability of the materials used to make the vaccine and conformation of the antigen, which in this case, is the spike protein, said Cowden.
She explained the SARS-CoV-2 virus requires a certain configuration of the spike protein so it can bind to ACE2 receptors, a type of enzyme, on human cells. “If the protein in the vaccine changes conformation so that that the [binding domain] RBD is not exposed, then the antibodies the body makes against the vaccine antigen won’t be targeted against it,” said Cowden. This may result in them not blocking the virus as well.