Dataset Information

Serum Neutralizing Antibody Titers 12 months after COVID-19 mRNA Vaccination: Correlation to Clinical Variables in an Adult, US-Population.

ABSTRACT:

Background

We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.

Methods

Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.

Results

After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19 + individuals (132-fold increase). Age >65 years (β=-0.94, p = 0.001) and malignancy (β=-0.88, p = 0.002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p = 0.004); (β=-0.66, p = 0.014)], diabetes mellitus [(β=-0.57, p = 0.032); (β=-0.44, p = 0.028)], and systemic steroid use [(β=-0.066, p = 0.032); (β=-0.55, p = 0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2. Post-booster neutralization increased with prior COVID-19 (β = 2.9, p-value < 0.0001), and malignancy reduced neutralization response (β=-0.68, p = 0.03), regardless of infection status.

Conclusion

Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.

SUBMITTER: Zhao M

PROVIDER: S-EPMC9278145 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Serum Neutralizing Antibody Titers 12 Months After Coronavirus Disease 2019 Messenger RNA Vaccination: Correlation to Clinical Variables in an Adult, US Population.

Zhao Min M Slotkin Rebecca R Sheth Amar H AH Pischel Lauren L Kyriakides Tassos C TC Emu Brinda B McNamara Cynthia C Shi Qiaosu Q Delgobbo Jaden J Xu Jin J Marhoffer Elizabeth E Mercer-Falkoff Aleagia A Holleck Jürgen J Ardito David D Sutton Richard E RE Gupta Shaili S

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20230201 3

<h4>Background</h4>We studied whether comorbid conditions affect strength and duration of immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccination in a US-based, adult population.<h4>Methods</h4>Sera (before and after BNT162b2 vaccination) were tested serially up to 12 months after 2 doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variabl ...[more]

PMID: 35639598

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Project description:BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) is dominating coronavirus disease 2019 (COVID-19) worldwide. The waning protective effect of available vaccines against the Omicron variant is a critical public health issue. This study aimed to assess the impact of the third COVID-19 vaccination on immunity against the SARS-CoV-2 Omicron BA.1 strain in older individuals.Materials and methodsAdults aged ≥60 years who had completed two doses of the homologous COVID-19 vaccine with either BNT162b2 (Pfizer/BioNTech, New York, NY, USA, BNT) or ChAdOx1 nCoV (SK bioscience, Andong-si, Gyeongsangbuk-do, Korea, ChAd) were registered to receive the third vaccination. Participants chose either BNT or mRNA-1273 (Moderna, Norwood, MA, USA, m1273) mRNA vaccine for the third dose and were categorized into four groups: ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273. Four serum specimens were obtained from each participant at 0, 4, 12, and 24 weeks after the third dose (V1, V2, V3, and V4, respectively). Serum-neutralizing antibody (NAb) activity against BetaCoV/Korea/KCDC03/2020 (NCCP43326, ancestral strain) and B.1.1.529 (NCCP43411, Omicron BA.1 variant) was measured using plaque reduction neutralization tests. A 50% neutralizing dilution (ND50) >10 was considered indicative of protective NAb titers.ResultsIn total, 186 participants were enrolled between November 24, 2021, and June 30, 2022. The respective groups received the third dose at a median (interquartile range [IQR]) of 132 (125 - 191), 123 (122 - 126), 186 (166 - 193), and 182 (175 - 198) days after the second dose. Overall, ND50 was lower at V1 against Omicron BA.1 than against the ancestral strain. NAb titers against the ancestral strain and Omicron BA.1 variant at V2 were increased at least 30-fold (median [IQR], 1235.35 [1021.45 - 2374.65)] and 129.8 [65.3 - 250.7], respectively). ND50 titers against the ancestral strain and Omicron variant did not differ significantly among the four groups (P = 0.57). NAb titers were significantly lower against the Omicron variant than against the ancestral strain at V3 (median [IQR], 36.4 (17.55 - 75.09) vs. 325.9 [276.07 - 686.97]; P = 0.012). NAb titers against Omicron at V4 were 16 times lower than that at V3. Most sera exhibited a protective level (ND50 >10) at V4 (75.0% [24/32], 73.0% [27/37], 73.3% [22/30], and 70.6% [12/17] in the ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273 groups, respectively), with no significant differences among groups (P = 0.99).ConclusionA third COVID-19 mRNA vaccine dose restored waning NAb titers against Omicron BA.1. Our findings support a third-dose vaccination program to prevent the waning of humoral immunity to SARS-CoV-2.