One dose of COVID-19 mRNA vaccine in SARS-CoV-2-experienced people may be sufficient

Background: Understanding if single doses of SARS-CoV-2 mRNA vaccines in SARS-CoV-2-experienced people are fully protective is a public health priority. This study measured immune responses before and after mRNA vaccine in people with or without histories of COVID-19. Methods: Specimens were collected from participants before and 6-14 days after doses 1 and 2. Humoral assays included an S1-specific Ig ELISA and a livevirus microneutralization assay (MN) vs the original SARS-CoV-2 USA-WA1/2020 strain. ELISpot assays and 36-color spectral analysis flow cytometry assessed B- and T-cell responses. Results: 32 adults received Pfizer BioNTech vaccine and 1 received Moderna vaccine. 14 had a history of COVID-19 (median age 41, 71% female, 10 with 3/20 and 2 with 12/20 illness onset, 2 asymptomatic). 19 were SARS-CoV-2-naive (median age 39, 47% female). S1-specific IgG/A/M ASC were detected readily by ELISpot 6-14 days after dose 1 and were higher in SARS-CoV-2-experienced (median: 200) than -naive (median: 27) subjects;after dose 2, the converse was observed (medians 53 vs 293). By flow cytometry, T cell activation was broadly observed 6-14 days after 1st vaccination, with increases in CD4+ or CD8+ T cells expressing CD38 and Ki67 (CD4: median fold-changes 1.6 for SARS-CoV-2-experienced and 1.8 for -naive;CD8: 3.1 and 2.2). S1-specific IgG was present at baseline in experienced subjects (median: 6320), peaked at 6-14 days post-dose 1 (median: 169000), and wasn't boosted by dose 2 (panel A). In naive participants, S1-specific IgG was not present at baseline, low at day 6-14 (median: 66), higher at day 21 (median: 27000), and boosted by dose 2 (median: 188000). Interestingly, by 6-14 days after dose 2, experienced and naive subjects had similar S1-specific IgG titers. The MN titers followed a similar pattern (panel B): in experienced subjects, striking increases after dose 1 (median: 9860) but no boosting by dose 2;in naive subjects, no neutralization was observed at 6-14 days, low titers were present at 21 days post-dose 1 (median: 43), with boosting after dose 2 (median: 513). Conclusion: People with a history of SARS-CoV-2 infection who received a single dose of mRNA vaccine produced binding and neutralizing antibody titers at 6-14 days that were similar to, or higher than, titers in SARS-CoV-2-naive people who had received 2 doses. Their titers were not boosted by a second dose. These findings support a hypothesis that SARS-CoV-2-experienced people may require only a single dose of mRNA vaccine.