Assessment of the Humoral Immune Response Following COVID-19 Vaccination in Healthcare Workers: A One Year Longitudinal Study

Abstract

The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Nevertheless, breakthrough infections were present in 6.65% of all participants, without any correlation with the previous level of anti-S/RBD IgG. Protection against the ancestral and Omicron variants is maintained at least three months after a booster in HCW, possibly reflecting a continuous antigenic stimulation in the professional setting.

Keywords: SARS-CoV-2; booster dose; breakthrough infections; healthcare workers; host factors; immune response; vaccination.

Figure 1

Dynamics of anti-SARS antibodies in vaccinated healthcare workers, Romania, 2021. Before the 9-month collection, 70.58% of study participants received a third dose of BNT162b2 mRNA vaccine (Pfizer-BioNTech). (A) Anti-NCP-IgG dynamic monitored from infection time, demonstrating a complete loss of antibodies 5 months post-infection; (B) The 12-month anti-S/RBD IgG antibody dynamic in individuals without a booster dose of BNT162b2 mRNA vaccine, showing an important decrease one year after vaccination, irrespective of the presence of a previous infection; (C) The 12-month anti-S/RBD IgG antibody dynamic in individuals who received three doses of BNT162b2 mRNA vaccine (at day 0, 3 weeks, and 8 months), showing the transitory effect of a booster dose after 3 months in naive individuals and a more persistent effect in those previously infected; (D) The 12-month IgA anti-spike dynamic in individuals without a booster dose of BNT162b2 mRNA, showing persistence only in those with a prior SARS-CoV-2 infection; (E) The 12-month IgA anti-spike dynamic in individuals with three doses of BNT162b2 mRNA vaccine, showing constantly increased levels in all participants after the booster dose. W/O, without; W, with. *** indicates p < 0.001.

Figure 2

Anti-S/RBD IgG antibodies levels in vaccinated healthcare workers with breakthrough SARS-CoV-2 infections. Comparative antibody levels were depicted for 12 months, showing similar IgG anti-spike levels in individuals with and without a breakthrough infection at the 6-month collection point, but significant lower initial antibody titers in those infected prior to vaccination who experience breakthrough infections (blue and green lines) compared to those who do not (black and red lines). A red arrow indicates the moment of infection in vaccinated individuals (all infections acquired during the Delta VOC wave in Romania). At 12 months post-vaccination, significantly higher antibody levels are present in all patients who experience breakthrough infections compared with those who remain uninfected (p < 0.001), with superior and more stable titers maintained in those uninfected prior to vaccination (p < 0.05). * indicates p < 0.05; ** indicates p < 0.01; *** indicates p < 0.001.

Figure 3

Host factors’ influence on anti-NCP IgG antibodies in healthcare workers, Romania, 2021. Influence of BMI (A), gender (B), age (C), disease form (D), and presence of comorbidities (E) was analyzed. N, normal weight; OW, overweight; OB, obese; W/O, without; W, with; F, female; M, male. ** indicates p < 0.01; **** indicates p ≤ 0.0001.

Figure 4

Host factors’ influence on the dynamics of anti-S/RBD IgG antibodies in healthcare workers, Romania, 2021. The influence of cofactors such as BMI (A), gender (B), age (C), COVID-19 disease form (D), presence of comorbidities (E), and type comorbidity (F) was analyzed. NCP negative (-), SARS-CoV-2 naïve; NCP positive (+), with prior SARS-CoV-2 infection; N, normal weight; OW, overweight; OB, obese; W/O, without; W, with; F, female; and M, male. * indicates p < 0.05; ** indicates p < 0.01; **** indicates p ≤ 0.0001.

Figure 5

Modeling waning immunity for HCW, Romania, 2021. Four distinctive dynamics patterns reported at the initial level: persistent (>90%), slow (60–89%), moderate (30–59%), and rapid waning (<30%). (A) Neutralizing antibody dynamics, measured by percentage of sVNT readings of sVNT. (B) Anti-S/RBD IgG levels measured in BAU/mL.