Long-Term Immunity against SARS-CoV-2 Wild-Type and Omicron XBB.1.5 in Indonesian Residents after Vaccination and Infection

Abstract

In the post-pandemic era, evaluating long-term immunity against COVID-19 has become increasingly critical, particularly in light of continuous SARS-CoV-2 mutations. This study aimed to assess the long-term humoral immune response in sera collected in Makassar. We measured anti-RBD IgG levels and neutralization capacity (NC) against both the Wild-Type (WT) Wuhan-Hu and Omicron XBB.1.5 variants across groups of COVID-19-vaccinated individuals with no booster (NB), single booster (SB), and double booster (DB). The mean durations since the last vaccination were 25.11 months, 19.24 months, and 16.9 months for the NB, SB, and DB group, respectively. Additionally, we evaluated the effect of breakthrough infection (BTI) history, with a mean duration since the last confirmed infection of 21.72 months. Our findings indicate fair long-term WT antibody (Ab) titers, with the DB group showing a significantly higher level than the other groups. Similarly, the DB group demonstrated the highest anti-Omicron XBB.1.5 Ab titer, yet it was insignificantly different from the other groups. Although the level of anti-WT Ab titers was moderate, we observed near-complete (96-97%) long-term neutralization against the WT pseudo-virus for all groups. There was a slight decrease in NC against Omicron XBB.1.5 compared to the WT among all groups, as DB group, SB group, and NB group showed 80.71 ± 3.9%, 74.29 ± 6.7%, and 67.2 ± 6.3% neutralization activity, respectively. A breakdown analysis based on infection and vaccine status showed that booster doses increase the NC against XBB.1.5, particularly in individuals without BTI. Individuals with BTI demonstrate a better NC compared to their counterpart uninfected individuals with the same number of booster doses. Our findings suggest that long-term immunity against SARS-CoV-2 persists and is effective against the mutant variant. Booster doses enhance the NC, especially among uninfected individuals.

Keywords: COVID-19 vaccines; Omicron XBB.1.5; antibodies; immune persistence; neutralizing capacity.

Figure 1

Schematic depiction of the vaccination timeline and breakthrough infections (BTI) for three groups based on booster status. The mean duration from the last vaccination to blood collection is 25.11 weeks for the no booster (NB) group, 19.24 weeks for the 1× booster (SB) group, and 16.9 weeks for the 2× booster (DB) group (p < 0.0001).

Figure 2

Anti-RBD IgG titer of SARS-CoV-2 Wild-Type (WT) and Omicron XBB.1.5. While the booster doses affect the persistence of antibody (Ab) titers against SARS-CoV-2 WT (A), they do not affect the persistence of anti-XBB.1.5 Ab titer (B). Breakthrough infections (BTI) resulted in higher titer against WT SARS-CoV-2 (C) but no significant differences in anti-XBB.1.5 titer compared to non-infected participants (D). The Ab titers based on infection status and vaccine are shown in (E) and (F). The Ab titers of individuals with BTI beyond 2021 against WT (E) and XBB.1.5 (F) are not significantly different from vaccinated individuals without BTI. The antibody titers were measured using indirect ELISA and are expressed as ELISA’s optical density (OD) measurements at 414 nm. Individual values are shown, and horizontal lines represent median and quartile of Ab titers. Statistical analyses were conducted using the Mann–Whitney test: **** p < 0.0001, ** p < 0.01.

Figure 3

A comparison of long-term neutralization capacity (NC). (A) Almost-complete NC against WT in all subjects. (B) Comparison of NC against XBB.1.5, with double booster (DB) groups having the highest NC compared to no booster (NB) and single booster (SB) groups. (C) Individuals with breakthrough infection (BTI) exhibit comparable NC against WT compared to the untested group. (D) Individuals with BTI demonstrate higher NC against XBB.1.5 than untested groups. (E,F) The effect of booster doses on WT NC and XBB.1.5 NC among individuals with confirmed BTI and those without BTI. Serum NC was measured using ONE-Glo EX^TM Luciferase Assay System. Individual values are shown with bars that represent the means and horizontal lines that represent SEM. Statistical analyses were performed using the Mann–Whitney U test, * p < 0.05.

Figure 4

Correlation between antibody (Ab) titer and either neutralization capacity (NC) or cross-neutralization. A similar weak relationship between serum Ab titers and their respective NC was observed for both Wild-Type (WT) (blue dots) (A) and Omicron XBB.1.5 (orange dots) (B). Cross-correlation analysis between WT Ab titers and Omicron XBB.1.5 internalization (C); and Omicron XBB.1.5 Ab titers and WT internalization (D). Serum Ab titers were measured using indirect ELISA and are expressed as optical density at 414 nm, while serum NC was measured with the ONE-Glo EX™ Luciferase Assay System. Red lines depict the non-linear regression model between variables.