One dose of mRNA vaccine may suffice for previously infected people
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Results from multiple studies suggest that halving the two-dose series of COVID-19 messenger RNA vaccines may be sufficient to protect people who have recovered from COVID-19.
The first study, presented at the virtual Conference on Retroviruses and Opportunistic Infections, assessed specimens collected from study participants before and 6 to 14 days after doses one and two of the messenger RNA (mRNA) vaccines.
“People with known past COVID-19 were excluded from the phase 3 efficacy trials of COVID-19 vaccines,” Mark J. Mulligan, MD, FIDSA, director of New York University Langone Health’s Vaccine Center, told Healio. “With rollout of the emergency use authorization (EUA) vaccines, we had the opportunity to compare vaccine responses in SARS-CoV-2-experienced people with those in naive people.”
The study included 21 adults who received the Pfizer-BioNTech vaccine and one who received the Moderna vaccine. According to Mulligan and colleagues, the 14 people included in the study “produced binding and neutralizing antibody titers at 6 to 14 days that were similar to, or higher than, titers in SARS-CoV-2-naive people who had received 2 doses.” Moreover, the researchers found that the titers were not boosted by a second dose of vaccine.
“Without prior infection, the first dose is important to establish memory, and the second dose is really important to increase avidity and increase antibody-secreting cells,” Mulligan explained.
Mulligan said it would be beneficial to compare one dose vs. two doses of the mRNA vaccines in people who have recovered from COVID-19 and assess their immune responses over time.
“At this time I do not advocate for a vaccination recommendation change. We don’t know enough yet,” he said. “Two doses of mRNA vaccines are the standard to follow for public health, as per the EUA.”
‘Requires investigation’
Florian Krammer, PhD, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York, and colleagues also assessed antibody responses in seropositive individuals following a single dose of mRNA vaccine.
They used the ongoing PARIS study to examine antibody responses in 110 individuals ⎼⎼ 67 seronegative and 43 seropositive ⎼⎼ who received a first dose of one of the vaccines.
According to the study, which was published in a letter Wednesday in The New England Journal of Medicine, “repeated sampling after the first dose indicates that the majority of seronegative participants had variable and relatively low SARS-CoV-2 IgG responses within 9 to 12 days after vaccination,” whereas participants who already had SARS-CoV-2 antibodies “rapidly developed uniform, high antibody titers within days after vaccination.”
Krammer and colleagues reported that the antibody titers of participants in the latter group “were 10 to 45 times as high as those of vaccinees without preexisting immunity at the same time points after the first vaccine dose … and also exceeded the median antibody titers measured in participants without preexisting immunity.”
They said antibody titers of the vaccinees without preexisting immunity increased by a factor of 3 after the second vaccine dose, but that no increase was observed among COVID-19 survivors following their second dose.
“We found that a single dose of mRNA vaccine elicited rapid immune responses in seropositive participants, with postvaccination antibody titers that were similar to or exceeded titers found in seronegative participants who received two vaccination,” they wrote. “Whether a single dose of mRNA vaccine provides effective protection in seropositive person requires investigation.”
Study in health care workers
A recent paper published in JAMA reported similar results among health care workers who had previously been infected and were subsequently vaccinated.
Saman Saadat, PhD, a post-doctorate fellow in the Institute of Human Virology at the University of Maryland School of Medicine, and colleagues assess results from hospitalwide serosurvey study conducted from July to August 2020 at the University of Maryland Medical Center.
According to the study, participants were randomly contacted based on stratification into three groups SARS-CoV-2 IgG antibody negative (Ab-negative), IgG positive asymptomatic COVID-19 (asymptomatic) and IgG positive with history of symptomatic COVID-19 (symptomatic) and were vaccinated with one of the two mRNA vaccines.
Of the 3,816 health care workers enrolled in the study, 151 were randomly contacted and 59 volunteers enrolled 17 in the Ab-negative group, 16 in the asymptomatic group and 26 in the symptomatic group. According to the study, at days 0, 7 and 14, median reciprocal half-maximal binding titers were higher in each of the asymptomatic (208, 29,364 and 34,033) and symptomatic (302, 32,301 and 35,460) groups compared with the Ab-negative group (<50, <50 and 924) (P < .001).
Additionally, the researchers found that at days 0 and 14, median reciprocal ID99 virus neutralization titers — “the 99% inhibitory dose, the highest dilution at which 99% of cells were protected” — of each of the asymptomatic (80 and 40,960) and symptomatic (320 and 40,960) groups were higher than the Ab-negative group (<20 and 80) (P < .001).
“Health care workers with previous COVID-19 infection, based on laboratory-confirmed serology testing, had higher antibody titer responses to a single dose of mRNA vaccine than those who were not previously infected,” Saadat and colleagues wrote. “Given the ongoing worldwide vaccine shortages, the results inform suggestions for a single-dose vaccination strategy for those with prior COVID-19 or placing them lower on the vaccination priority list.”
References:
Krammer F, et al. New Engl J Med. 2021;doi:10.1056/NEJMc21.1667.
Saadat S, et al. JAMA. 2021;doi:10.1001/jama.2021.3341.
Samanovic-Golden MI, et al. Abstract 119LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 6-10, 2021 (virtual meeting).
Perspective
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At a crucial time in this pandemic, when vaccines are now available to us albeit in limited supply, at least at the outset judicious use of resources must be a priority. This adds to emerging evidence to provide grounds to consider requiring only a single dose of mRNA vaccine for those infected previously with SARS-CoV-2. Single-dose administration of vaccines to previously infected patients is an attractive consideration, not just from the individual point of view eg, logistics of two doses, side effects, etc. but also will enable acceleration of higher level of immunity in the population to help us climb out of this pandemic sooner if this approach is reasonably proved to impart a sufficient level of immunity. Of course, further data and larger studies will certainly be vital to making any changes in recommendations to the current two-dose regimens as they were studied in their respective large-scale clinical trials.
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Samanovic-Golden MI, et al. Abstract 119LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 6-10, 2021 (virtual meeting).
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