Long-term, infection-acquired immunity against the SARS-CoV-2 Delta variant in a hamster model

Abstract

The emergence of the SARS-CoV-2 Delta variant (B.1.617.2) raises concerns about potential reduced sensitivity of the virus to antibody neutralization and subsequent vaccine breakthrough infections. Here, we use a live virus neutralization assay with sera from Pfizer- and Moderna-vaccinated individuals to examine neutralizing antibody titers against SARS-CoV-2 and observe a 3.9- and 2.7-fold reduction, respectively, in neutralizing antibody titers against the Delta variant compared with an early isolate bearing only a D614G substitution in its spike protein. We observe similar reduced sensitivity with sera from hamsters that were previously infected with an early isolate of SARS-CoV-2. Despite this reduction in neutralizing antibody titers against the Delta variant, hamsters previously infected (up to 15 months earlier) with an early isolate are protected from infection with the Delta variant, suggesting that the immune response to the first infection is sufficient to provide protection against subsequent infection with the Delta variant.

Keywords: B.1.617.2; Delta variant; SARS-CoV-2; antibody sensitivity; re-infection; transmission.

Graphical abstract

Figure 1

Antibody responses to the Delta variant (A and B) Neutralization antibody titers (A) and fold-changes (B) using human sera obtained from individuals vaccinated twice with either the Pfizer vaccine (30 samples) or the Moderna vaccine (17 samples). Neutralization assays were performed once with an isolate of SARS-CoV-2 with only the D614G mutation in the spike protein (HP095 S-614G) or with an isolate of the Delta variant. Fold-changes in neutralization titers for the Delta variant (B; indicated in parentheses) using the same vaccine serum samples compared against the HP095 S-D614G virus. The bars indicate the geometric mean.

Figure 2

Virus titers of the Delta variant in hamsters (A–D) Virus replication in groups of naive hamsters (A and C) or groups of hamsters previously infected with WA-1 S-614D (B) or NCGM02 S-614D (D) and re-infected with the same virus or the Delta variant. Black dots represent individual titers from one study and those on the x axis represent virus titers below the limit of detection (10 pfu/g). The bars represent the mean titer for each group There were no significant differences between virus titers in any of the groups shown (p < 0.05).

Figure 3

Transmission of the Delta variant between hamsters (A–D) Virus replication in naive hamsters infected with the Delta variant (A) and their exposed cage mates (B), or hamsters previously infected with WA-1 S-614D and re-infected with the Delta variant (C) and their exposed cage mates (D). Black dots represent individual titers from one study and those on the x axis represent virus titers below the limit of detection (10 pfu/g). The bars represent the mean titer for each group. Nasal wash (NW); day (D); nasal turbinate (NT). There were no significant differences between virus titers in any of the groups shown (p < 0.05).