immune responses SARS-CoV-2 delta variant

A large cluster of coronavirus disease 2019 (COVID-19) infections were reported to the Massachusetts Department of Public Health (MA DPH) following the weekend of July 4, 2021 in Provincetown, Barnstable County, Massachusetts ( 1). About 74% of cases occurred in people fully vaccinated with the COVID-19 vaccines BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Johnson & Johnson) (2–4). Most cases were reported as mildly or moderately symptomatic.

Viral sequencing revealed that more than 90% of sequenced cases were the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and viral loads in nasal swabs were similar in vaccinated and unvaccinated people ( 1). This outbreak was the first known large cluster of SARS-CoV-2 delta variant infections in a highly vaccinated population, and it prompted the US Centers for Disease Control and Prevention to reinstate indoor masking recommendations. for fully vaccinated people.

Here, we recruited vaccinated individuals who were part of the MA DPH outbreak investigation or enhanced surveillance and who tested positive or negative for COVID-19 by nasopharyngeal swabs. These people participated in a detailed immunological study at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts. We measured peripheral antibody responses, mucosal antibody responses, and cellular immune responses in this cohort of vaccinated individuals with or without breakthrough SARS-CoV-2 infection.

A total of 39 individuals from the MA DPH outbreak investigation (1) were recruited, including 16 vaccinees who tested positive for SARS-CoV-2 and 23 vaccinees who tested negative for SARS-CoV-2. SARS-CoV-2 (Table S1). The participants were predominantly white and most were male. Vaccinated infected individuals were generally younger (median age, 38 years; range, 25 to 60) than vaccinated uninfected individuals (median age, 61 years; range, 24 to 77).

Participants received BNT162b2 (Pfizer; n=16), mRNA-1273 (Moderna; n=22), or Ad26.COV2.S (Johnson & Johnson; n=1) vaccines. Peripheral blood and nasal swab specimens were obtained for immunoassays at a median of 189 days (range, 127 to 251) after the first vaccine dose and at a median of 34 days (range, 0 to 67) after SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) testing as part of the outbreak investigation.

In the vaccinated infected group, 15 of 16 (94%) people reported symptoms of COVID-19 infection, most commonly respiratory symptoms, fever, and loss of smell or taste, according to the overall outbreak investigation (1); all had asymptomatic or mild disease according to the National Institutes of Health (NIH) disease severity classification, and none required hospitalization. Samples from a separate cohort of 18 unvaccinated infected individuals with mild disease were also obtained for comparison (Table S2).

Humoral immune responses after exposure to the delta variant

Serum SARS-CoV-2 antibody responses were assessed by spike and nucleocapsid-specific electrochemiluminescence (ECLA) assays, receptor-binding domain (RBD)-specific enzyme immunoassays (RBD ) immunoglobulin G (IgG) and pseudovirus neutralization antibody assays.

SARS-CoV-2 WA1/2020 spike protein-specific ECLA titers, B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta) and B.1.617.1 (kappa) variants were 14, 15, 11, 18, 15 and 22 times higher, respectively, in vaccinated infected individuals compared to vaccinated uninfected individuals (P < 0.001 for all variants , Wilcoxon rank sum tests; Fig. 1A).

Core-specific ECLA responses were detected in all but one vaccinated infected participant, consistent with SARS-CoV-2 infection, and in none of the uninfected participants (P < 0.001, rank sum tests from Wilcoxon; Fig. 1B). RBD-specific IgG ELISA titers against SARS-CoV-2 WA1/2020, B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma).

B.1.617.2 (delta) and Les B.1.617.1 (kappa) variants were 17, 21, 31, 25, 32, and 23 times higher, respectively, in infected vaccinated individuals than in uninfected vaccinated individuals (P < 0.001 for all variants, Sum tests Wilcoxon rows; Fig. 1C). Pseudovirus neutralizing antibody titers against RAS alpha, beta, and delta variants