In what is believed to be one of the largest studies of its kind, Johns Hopkins Medicine researchers have shown that antibody levels against SARS-CoV-2 (the COVID-19 virus) stay more durable, that is, remain higher over an extended period of time, in people who were infected by the virus and then received protection from two doses of messenger RNA (mRNA) vaccine compared with those who only got immunised.
A research letter detailing this study of nearly 2,000 health care workers appeared on Monday 1 November 2021 in the Journal of the American Medical Association (JAMA).
“This finding adds to our understanding of how immunity against SARS- CoV-2 works, and builds upon an earlier study by our team that showed the mRNA vaccines yielded a robust antibody response, even if a person did not develop significant symptoms following vaccination or did not have a prior SARS-CoV-2 infection,” said study senior author Dr Aaron Milstone, professor of paediatrics at the Johns Hopkins University School of Medicine and paediatric epidemiologist at Johns Hopkins Children’s Centre.
The two mRNA vaccines evaluated in the study introduce the body’s immune system to S1, a protein subunit that’s a component of the spikes found on the surface of SARS-CoV-2. The spikes enable the virus to latch on to healthy cells and infect them.
Immunoglobulin G antibodies, elicited by S1 from the vaccines stimulating the immune system, neutralise the virus particles, preventing infection by SARS-CoV-2, or at least, reducing the severity of the disease.
For their latest study, the researchers followed 1,960 Johns Hopkins Medicine healthcare workers who had received both doses of either the Pfizer/BioNTech or Moderna vaccines, including 73 people who had a positive SARS-CoV-2 polymerase chain reaction (PCR) test result before the first vaccine dose. The 73 were divided into two groups, those who were infected at 90 days or closer to the first vaccine dose, and those whose exposure to the virus was more than 90 days before the initial shot.
After adjusting for vaccine type, age and sex, antibody levels were compared for those with and without prior SARS-CoV-2 infection at one, three and six months after the second vaccine dose. In addition, antibody levels were compared at one and three months following the second dose between the two groups with prior SARS-CoV-2 infection.
“We found that healthcare workers with prior SARS-CoV-2 infection followed by two doses of mRNA vaccine, therefore, three independent exposures to the S1 spike protein, developed higher antibody levels than those with vaccination alone,” said study lead author Dr Diana Zhong, an infectious diseases fellow at the Johns Hopkins University School of Medicine.
“The relative differences were 14% higher at one month after the second vaccine dose, 19% at three months and 56% at six months.” Zhong added that the study participants with a PCR-confirmed SARS-CoV- 2 infection more than 90 days before their initial vaccination had adjusted antibody levels 9% (one month after the second vaccine dose) and 13% (three months after the second vaccine dose) higher than those who were exposed to the virus less than or equal to the 90-day mark.
“This suggests that a longer interval between infection and first vaccine dose may enhance the antibody response,” said Milstone, adding that further investigation was needed to determine whether increased post-vaccination durability in previously infected people is attributable to the number of exposures to the virus, the interval between exposures, or the interplay between natural or vaccine-derived immunity.
Study details
Durability of Antibody Levels After Vaccination With mRNA SARS-CoV-2 Vaccine in Individuals With or Without Prior Infection
Diana Zhong, Shaoming Xiao, Aaron Milstone, Amanda Debes, Emily Egbert, Patrizio Caturegli and Elizabeth Colantuoni.
Published in JAMA on 1 November 2021
Waning serum antibodies against SARS-CoV-2 have raised questions about long-term immunity. Lower antibody levels to SARS-CoV-2 spike protein are associated with breakthrough infections after vaccination, prompting consideration of booster doses. Prior infection may enhance protection from vaccination, stimulating inquiry about hybrid immunity. Our objective was to examine SARS-CoV-2 spike IgG antibodies in a longitudinal cohort, comparing antibody durability in individuals who received an mRNA SARS-CoV-2 vaccine with or without prior SARS-CoV-2 infection.
Methods
A convenience sample of 3,500 health care workers from the Johns Hopkins Health System were enrolled starting June 2020 and followed up until 3 September 2021. Participants provided serum samples longitudinally, separated by at least 90 days. SARS-CoV-2 polymerase chain reaction (PCR) test results and vaccination dates (inside and outside the health system) were collected from electronic health records. Included participants had a serum sample collected at least 14 days after receiving the second dose of an mRNA SARS-CoV-2 vaccine.
Previous SARS-CoV-2 infection was defined by the date of positive SARS-CoV-2 PCR test results prior to first vaccine dose. IgG antibody measurements were obtained using an enzyme-linked immunosorbent assay (Euroimmun), estimating optical density ratios with a lower threshold of 1.23 and upper threshold of 11.00 based on assay saturation.
Linear regression models for log-transformed postvaccination antibody measurements were used to compare absolute and relative differences in median antibody measurements among health care workers with or without prior SARS-CoV-2 infection at 1, 3, and 6 months and health care workers with PCR-confirmed prior SARS-CoV-2 infection less than or equal to 90 days and greater than 90 days before receipt of the vaccine at 1 and 3 months, after adjusting for vaccine type, age, and sex. Statistical significance was defined as a 95% CI that did not include 1.00 for the relative adjusted median and a 95% CI that did not include 0 for the absolute difference in adjusted median. Analyses were performed in R software, version 4.0.2 (R Foundation).
Results
Of the 1,960 healthcare workers who provided serum samples at least 14 days after receipt of the second vaccine dose, 73 (3.7%) had evidence of previous infection (41 with positive PCR results ≤90 days before vaccination and 32 with positive PCR results >90 days before vaccination). Of these 1960 participants, 80% were women, 95% were non-Hispanic/Latino, and 80% were white. The median (IQR) age of participants was 40.4 (32.6-52.1) years.
Among participants without previous SARS-CoV-2 infection, the adjusted median antibody measurements were 8.69 (95% CI, 8.56-8.80) at 1 month, 7.28 (95% CI, 7.15-7.40) at 3 months, and 4.55 (95% CI, 4.16-4.91) at 6 months after vaccination. Compared with participants without previous SARS-CoV-2 infection, those with prior infection maintained higher postvaccination adjusted median antibody measurements by an absolute difference of 1.25 (95% CI, 0.86-1.62) (relative difference, 14% [95% CI, 10%-19%]) at 1 month, 1.42 (95% CI, 0.98-1.86) (relative difference, 19% [95% CI, 13%-26%]) at 3 months, and 2.56 (95% CI, 1.66-4.08) (relative difference, 56% [95% CI, 35%-94%]) at 6 months.
Individuals with PCR-confirmed infection more than 90 days before vaccination had higher post-vaccination adjusted antibody measurements, compared with those with PCR-confirmed infection less than or equal to 90 days before vaccination, of 10.52 (95% CI, 10.13-11.00) (absolute difference, 0.86 [95% CI, 0.28-1.48]; relative difference, 9% (95% CI, 3%-16%]) at 1 month and 9.31 (95% CI, 8.47-9.98) (absolute difference, 1.09 [95% CI, 0.17-1.92]; relative difference, 13% [95% CI, 2%-24%]) at 3 months
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