key: cord-0815784-i6et6ja9
authors: Fedele, Giorgio; Palmieri, Annapina; Malara, Alba; Damiano, Cecilia; Di Lonardo, Anna; Schiavoni, Ilaria; Leone, Pasqualina; Panduri, Giuseppina; Minchella, Pasquale; Talarico, Francesco; Palamara, Anna Teresa; Stefanelli, Paola; Incalzi, Raffaele Antonelli; Onder, Graziano
title: A third dose of mRNA COVID-19 vaccine significantly enhances anti-SARS-CoV-2 Spike IgG response in nursing home residents in Italy.
date: 2022-05-16
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2022.05.006
sha: 61d7a691c9a5bdc16f0a35bfe5a766d8fa7b1840
doc_id: 815784
cord_uid: i6et6ja9

A third dose of mRNA COVID-19 vaccine dose restores high levels of anti-Spike IgG in nursing home residents. A longer interval between first and third dose does not impair immunogenicity.

To the editor, 1 A rapid development of effective vaccines against severe acute respiratory syndrome coronavirus 2 2 (SARS-CoV-2) infection and their deployment has proved to be a highly successful strategy to reduce the 3 impact of COVID-19 pandemic 1 . Several studies have suggested a waning of humoral responses after 4 primary vaccination 2-4 . A third dose of the mRNA vaccine was shown to increase neutralizing antibody levels 5 and prevent severe outcomes 5,6 . However, data on the response to third dose of SARS-CoV-2 vaccine in frail 6 and complex population in NH are still limited. In this context, we have assessed the trajectories of humoral 7 immunity in a sample NH resident receiving a three-dose SARS-CoV-2 vaccine schedule. 8

Data are from the GeroCOVID VAX project, a study promoted by [blinded for review] and the [blinded 9

for review] and sponsored by the [blinded for review]. 7 We present data based on a subsample of 144 10 residents with no clinical history of SARS-CoV-2 infection from 14 NH in Calabria Region in Italy. All 11 participants received two doses of BNT162b2 vaccine 3 weeks apart and a third dose of an mRNA vaccine 12 (either mRNA-1273 or BNT162b2) between 6 and 9 months from the first vaccine dose 7 . Humoral immunity 13 was assessed by the Liaison® SARS-CoV-2 TrimericS IgG assay (DiaSorin, Italy) on serum samples collected at 14 4 time-points: prior to the first dose of vaccine (T0); 2 months after first vaccine dose (T1); 6 months after 15 first vaccine dose (T2); 2 months after third dose (T3). T2 assessment was always performed before the third 16 dose. IgG antibody concentrations were expressed as binding antibody units (BAU/ml). According to 17 manufacturer's instructions, values ≥ 33.8 BAU/ml were interpreted as positive. Given the nonnormal 18 distribution of SARS-CoV-2 trimeric S IgG antibody concentrations, statistical analyses were performed using 19 log-transformed values and Geometric Means (GM) were calculated. Analysis of variance was used to 20 compare the GM across the four time-points. T1 was used as reference group. Differences in GM at T3 were 21 tested across sex, age groups and time from first vaccination. 22

The study was approved by the Italian National Ethical Committee with the permission number 264/2021 23 (January 26, 2021). 24

Median age of 144 study participants was 85.2 years and 104 (72.2%) were female. Participants were 25 vaccinated with two doses of BNT162b2. A third vaccination was administered with BNT162b2 (n=130) or 26 mRNA-1273 (n=14) between 6 and 9 months after the first dose. The rate of participants with anti-trimeric S 27 IgG levels above the positivity cut-off of the serological test raised from 0% at T0 (prior to first dose) to 99% 28 at T1 (1 month after second dose) and then declined to 81% at T2 (5 months after the second dose). At T3, 29 two months after the third dose all participants (100%) exceeded the positivity threshold. As shown in Table  30 1, SARS-CoV-2 TrimericS IgG concentration at T1 was significantly higher than those observed at T0 and T2, 31 but significantly lower than that measured at T3. A similar trend was observed in men and women and in 32 both age groups considered. When GM differences were tested across sex and age groups for T3, we 33 observed that participants aged < 80 years had higher antibody levels as compared with those aged ≥ 80 34 years (GM=4832.0 vs. 3272.8 BAU/mL), but this association did not reach statistical significance (p=0.08). No substantial difference was observed according to sex. Among participants receiving the third dose 8-9 months 36 after first dose (n=114), GM at T3 was higher (3775.2 BAU/ml; SE=400.9) as compared with those receiving 37 third dose 6-7 months after first dose (n=30) (2996.7 BAU/ml; SE=620.4), although not significant (p=0.32). 38

The present study shows that, among NH residents in Italy without prior SARS-CoV-2 infection, a third 39 dose of mRNA SARS-CoV-2 vaccines significantly enhances the antibody response to the Spike protein, even 40 in those residents above 80 years of age. Therefore, we confirm and reinforce findings of a previous study 41 suggesting a strong and rapid decay of humoral immunity after the second BNT162b2 dose and a high 42 antibody response after the third dose validate 5 . Moreover, our data show that an extended interval between 43 the first and the third dose did not result in impaired immunogenicity, thus adding relevant information for Table 1 . Geometric means (GM) and Standard Errors (SE) of SARS-CoV-2 TrimericS IgG serum concentration 108 (BAU/mL) at baseline assessment (prior to vaccination -T0), 2 and 6 months after first dose (T1 and T2), and 109 2 months after third dose (T3) in nursing home residents. All participants received two doses of BNT162b2 110 vaccine 3 weeks apart and a third dose of an mRNA vaccine (mRNA-1273 or BNT162b2) between 6 and 9 111 months from the first vaccine dose. GM were compared across the four time points (T1 is the reference 

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