Antibody Titers and Protection against Omicron (BA.1 and BA.2) SARS-CoV-2 Infection.

The emergence of the SARS-CoV-2 variants of concern has greatly influenced the immune correlates of protection, and there are little data about the antibody threshold concentrations to protect against infection with SARS-CoV-2 Omicron BA.1 or BA.2. We analyzed the antibody responses of 259 vaccinated healthcare workers, some of whom had been previously infected by SARS-CoV-2. The median follow-up was 179 days (IQR: 171-182) after blood collection. We detected 88 SARS-CoV-2 Omicron infections during the follow-up period, 55 (62.5%) with SARS-CoV-2 BA.1, and 33 (37.5%) with SARS-CoV-2 BA.2. A neutralizing antibody titer below 8 provided no protection against a BA.1 infection, a titer of 16 or 32 gave 73.2% protection, and a titer of 64 or 128 provided 78.4% protection. Conversely, the BA.2 infection rate did not vary as a function of anti-BA.2 neutralizing antibody titers. Binding antibody concentrations below 6000 BAU/mL provided no protection against Omicron BA.1 infection, 6000-20,000 BAU/mL provided 55.6% protection, and 20,000 or more provided 87.7% protection. There was no difference in BA.2 infection depending on the binding antibody concentration. Further studies are needed to investigate the relationship between antibody concentrations and infection with the Omicron BA.4/5 variants that are becoming predominant worldwide.

Decreased Efficiency of Neutralizing Antibodies from Previously Infected or Vaccinated Individuals against the B.1.617.2 (Delta) SARS-CoV-2 Variant.

The neutralizing antibody response is a key component of adaptive immunity and a primary protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The increased transmissibility of the SARS-CoV-2 Delta variant and its capacity to cause more severe disease could be linked to a significant reduction in neutralizing antibodies generated during a previous infection or vaccination. We analyzed blood samples from 162 unvaccinated health care workers (HCWs) collected 1 to 3 months postinfection and from 263 vaccinated health care workers 1 month after the last injection. We have compared the neutralizing antibody titers obtained using two virus strains, B.1.160 and B.1.617.2 (Delta variant). Binding antibody concentrations were measured by an immunoassay. The median neutralizing antibody titer against the B.1.160 strain was 128 (interquartile range [IQR], 16 to 256) and 32 (IQR, 8 to 128) against the Delta variant. To obtain a neutralizing antibody titer of 32 or 64, a binding antibody concentration of 182 binding antibody units (BAU)/mL (IQR, 81 to 974) was required with the strain B.1.160, while a concentration of 2,595 BAU/mL (IQR, 1,176 to 5,353) was required with the Delta variant. Our data indicate that antibodies neutralize the SARS-CoV-2 Delta variant 4 times less efficiently than they neutralize an earlier strain. Half of the HCWs had decreased protection from 94% to 76.8% or less for the same total antibody concentration. But neutralization might be correlated with other immune responses. The contributions of other responses, such as those of the T cell and B cell systems, to protection require further investigation. IMPORTANCE Recent studies showed that the neutralizing antibody titer is an important contributor to protection against SARS-CoV-2. With the emergence of new variants, the question arises of maintaining the neutralizing capacities of vaccines and/or of a past infection. We had protective data associated with total antibody concentrations and neutralizing antibody titers for a B.1.160 strain. We showed that to maintain the same levels of protection and, therefore, the same levels of neutralizing antibodies, a total antibody concentration 8.5 times greater is required with the Delta strain. (This study has been registered at ClinicalTrials.gov under registration no. NCT04385108.).