COVID-19 vaccines may produce distinct immune responses in HAE: Study
Future studies will look at how different antibodies could influence disease
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Different types of COVID-19 vaccines may produce distinct long-term immune responses in people with hereditary angioedema (HAE), according to a small study of four patients.
Researchers found that all participants developed antibodies against SARS-CoV-2 — the virus that causes COVID-19 — after vaccination, regardless of the vaccine they received. However, one patient developed an unusual pattern of antibodies.
“Our study was an individual-level observation,” researchers wrote, noting that studies are planned to understand how different antibodies could influence the disease.
The study, “Patterns of spike-specific IgG subclasses after different types of COVID-19 vaccines in patients with hereditary angioedema due to C1 inhibitor deficiency,” was published in Biomolecular Concepts.
COVID-19 generally did not worsen the course of HAE in earlier study
A type of angioedema, HAE is most often caused by mutations in a gene that carries instructions for making a protein called C1 esterase inhibitor (C1-INH). In HAE type 1, the body produces too little C1-INH, while in HAE type 2, the protein does not work properly.
C1-INH helps regulate production of bradykinin, a signaling molecule that increases blood vessel permeability. Without enough functional C1-INH, bradykinin levels can rise too high, allowing fluid to leak from blood vessels into surrounding tissues and triggering swelling attacks that can affect virtually any part of the body.
During SARS-CoV-2 infection, both activation of the complement system — part of the immune system — and elevated bradykinin levels can increase blood vessel permeability. This led researchers to initially hypothesize that people with HAE might be at greater risk of severe COVID-19 or more frequent swelling attacks.
However, later studies painted a more reassuring picture. The research team previously reported that COVID-19 generally did not become more severe or worsen the course of HAE in Hungarian patients. Vaccination against SARS-CoV-2 was also safe and produced antibody responses against the virus that were comparable to those seen in healthy individuals.
However, whether different types of COVID-19 vaccines produce different long-term antibody profiles “has not yet been investigated in HAE patients,” the researchers wrote.
One participant showed a distinct antibody profile
To address the gap, researchers analyzed blood samples from four adults with HAE type 1 who had received different COVID-19 vaccinations.
One participant, a 39-year-old woman, received three doses of Pfizer-BioNTech’s mRNA vaccine before later becoming infected with SARS-CoV-2. These vaccines work by delivering genetic instructions that prompt the body’s cells to temporarily make the spike protein, which the virus uses to enter human cells. The immune system then learns to recognize the spike protein and produce antibodies against it.
Two participants — a 37-year-old man and a 58-year-old woman — received two doses of Sputnik V, a viral vector vaccine, followed by a Pfizer-BioNTech booster. Viral vector vaccines also teach the body to make the spike protein, but they deliver the genetic instructions using a harmless, modified virus rather than the fatty particles used in mRNA vaccines. Neither participant reported a SARS-CoV-2 infection.
The fourth participant, a 62-year-old man, received two doses of Sinopharm’s inactivated-virus vaccine, followed by a Pfizer-BioNTech booster. Unlike mRNA and viral vector vaccines, inactivated vaccines contain whole virus particles that have been killed so they cannot cause disease, allowing the immune system to recognize multiple viral proteins. He also reported no SARS-CoV-2 infection.
The researchers measured antibodies directed against the virus’ spike protein. Rather than looking only at the total amount of antibodies produced, they also examined the four subclasses of IgG, the most abundant type of antibody in the bloodstream. Although all IgG antibodies help defend against infection, each subclass has slightly different immune functions.
All four participants had detectable spike-specific IgG antibodies 10 to 11 months after completing their first vaccination, with antibody levels falling within the range previously observed in healthy vaccinated Hungarian volunteers. IgG1, the subclass typically generated after viral infections and vaccination, accounted for the largest share of antibodies in every patient.
One participant showed a distinct antibody profile. In the woman who received three doses of Pfizer-BioNTech’s mRNA vaccine and later developed COVID-19, IgG4 accounted for 40.8% of all spike-specific IgG antibodies. By comparison, IgG4 accounted for up to 2.8% of spike-specific antibodies in the other three participants. IgG4 is typically produced only after repeated or prolonged exposure to the same antigen — the foreign substance that triggers an immune response — in this case, the virus’ spike protein.
Because the study included only four participants, the researchers emphasized that these findings represent individual observations. They said future studies are planned to examine whether these spike-specific IgG subclasses differ in their ability to activate the complement system, which could influence the disease course.
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