New research demonstrates a significant increase in immune response, up to four times, when alternating arms for multi-dose vaccinations, such as the COVID-19 vaccine. This finding, which emerged from a study involving 947 participants and published in The Journal of Clinical Investigation, challenges previous assumptions that arm choice does not affect immunization effectiveness, with implications for enhancing vaccine efficacy against variants like omicron.
COVID-19 vaccine discovery could shape clinical practices globally.
New research reveals as much as a four-fold increase in immune response when people alternate from one arm to the other when given a multi-dose vaccine.
The laboratory study led by researchers at Oregon Health & Science University measured the antibody response in the blood of 947 people who received two-dose vaccinations against COVID-19First identified in 2019 in Wuhan, China, COVID-19, or Coronavirus disease 2019, (which was originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–22 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>COVID-19 early in the pandemic. Participants included OHSU employees who agreed to enroll in research while getting vaccinated against the SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>SARS-CoV-2 virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>virus, and were randomized to get the second dose in either the same or the opposite arm as the first dose.
The study was recently published in The Journal of Clinical Investigation.
Historically, clinicians thought that arm choice didn’t matter.
The new study tested serum samples collected at various times after vaccination. They found a substantial increase in the magnitude and breadth of the antibody response among people who had “contralateral” — or a shot in each arm — boosting compared with those who did not.
The improved response clearly materialized three weeks after the second booster and persisted beyond 13 months after boosting. Investigators found heightened immunity to the original SARS-CoV-2 strain, and an even stronger immune response to the omicron variant that emerged roughly a year after arm alternation.
Researchers aren’t sure why this happens, but they speculate that giving a shot in each arm activates new immune responses in different lymph nodes in each arm.
“By switching arms, you basically have memory formation in two locations instead of one,” said senior author Marcel Curlin, M.D., associate professor of medicine (infectious diseases) in the OHSU School of Medicine and medical director of OHSU Occupational Health.
Laboratory research yields eye-opening results
OHSU had the opportunity to examine the question as part of a series of laboratory studies using blood drawn from willing employees beginning early in the COVID-19 pandemic. That line of research has produced a series of published studies related to the durability, breadth and potency of immune response following vaccination and breakthrough infections.
After vaccines became available in late 2020, some participants wondered whether it made a difference if they alternated arms in the two-dose regimen.
“This question hasn’t really been extensively studied, so we decided to check it out,” Curlin said. “It turned out to be one of the more significant things we’ve found, and it’s probably not limited to just COVID vaccines. We may be seeing an important immunologic function.”
Among the people in the study who agreed to switch arms, researchers matched 54 pairs for age, gender, and relevant time intervals between vaccination and exposure — half getting the two doses in one arm and half in both.
Two weeks after the second dose, researchers didn’t see much of a difference in immune response. After three weeks, however, researchers measured significantly greater numbers of antibodies capable of binding and neutralizing the SARS-CoV-2 virus in blood samples. The rates progressively increased over four weeks from 1.3-fold to as much as a 4-fold increase against the omicron variant of the virus.
“Any incremental improvement might save a lot of lives,” Curlin said.
Further research needed
At this point, most people have long since been exposed to the SARS-CoV-2 virus multiple times either through vaccination, infection, or both.
Although the new study focused on vaccination against COVID-19, researchers say they expect the improved immune response could be similar for other multidose vaccinations. They call for further research to determine whether contralateral vaccination improves immune response for other vaccines, and especially among children.
“Several prime-boost vaccine regimens are essential components of pediatric care, and immune responses may differ in children,” they write.
Curlin said further study is needed and it is too soon to make clinical recommendations based on the results of this study. If and when a new virus emerges requiring a new two-dose vaccine, Curlin said he won’t hesitate.
“I’m going to switch up my arms,” he said.
Reference: “Contralateral second dose improves antibody responses to a two-dose mRNA vaccination regimen” by Sedigheh Fazli, Archana Thomas, Abram E. Estrada, Hiro A.P. Ross, David Xthona Lee, Steven Kazmierczak, Mark K. Slifka, David Montefiori, William B. Messer and Marcel E. Curlin, 16 January 2024, The Journal of Clinical Investigation.
DOI: 10.1172/JCI176411
The study was supported by the M.J. Murdock Charitable Trust; the OHSU Foundation; and the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>National Institutes of Health award R01AI145835 and P51OD011092.
Source: SciTechDaily
