Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine

Furukawa, Koichi; Tjan, Lidya Handayani; Kurahashi, Yukiya; Sutandhio, Silvia; Nishimura, Mitsuhiro; Arii, Jun; Mori, Yasuko

doi:10.1001/jamanetworkopen.2022.10780

Cited by 31 publications

(25 citation statements)

References 71 publications

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“…Higher humoral immune responses as determined by antispike-antibody determinations and sVNT tests have been reported for boostered vaccinees by several studies ( 15 – 20 ). Additionally, a higher immune response in boostered vaccinees compared to individuals, who only have been vaccinated twice, against the Omicron variant, which nevertheless is weaker than against the wild type virus, has been reported as well ( 21 , 22 ). However, no thresholds for a higher probability of SARS-CoV-2 breakthrough infection have been established based on other comprehensive longitudinal studies so far.…”

Section: Discussionmentioning

confidence: 99%

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections

et al. 2022

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BackgroundDespite the high level of protection against severe COVID-19 provided by the currently available vaccines some breakthrough infections occur. Until now, there is no information whether a potential risk of a breakthrough infection can be inferred from the level of antibodies after booster vaccination.MethodsLevels of binding antibodies and neutralization capacity after the first, one and six month after the second, and one month after the third (booster) vaccination against COVID-19 were measured in serum samples from 1391 healthcare workers at the University Hospital Essen. Demographics, vaccination scheme, pre-infection antibody titers and neutralization capacity were compared between individuals with and without breakthrough infections.ResultsThe risk of developing an Omicron breakthrough infection was independent of vaccination scheme, sex, body mass index, smoking status or pre-existing conditions. In participants with low pre-infection anti-spike antibodies (≤ 2641.0 BAU/ml) and weaker neutralization capacity (≤ 65.9%) against Omicron one month after the booster vaccination the risk for developing an Omicron infection was 10-fold increased (P = 0.001; 95% confidence interval, 2.36 - 47.55).ConclusionRoutine testing of anti-SARS-CoV-2 IgG antibodies and surrogate virus neutralization can quantify vaccine-induced humoral immune response and may help to identify subjects who are at risk for a breakthrough infection. The establishment of thresholds for SARS-CoV-2 IgG antibody levels identifying “non”-, “low” and “high”-responders may be used as an indication for re-vaccination.

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Section: Discussionmentioning

confidence: 99%

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections

et al. 2022

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“…SARS-CoV-2 omicron-B.1.1.529 led to widespread escape from neutralizing antibody responses [34]. A study in Japan reported that two doses of the BNT162b2 mRNA vaccine did not induce sufficient neutralizing antibodies against the omicron variant compared with other variants [35]. The frequency of CD4+ T cells and CD8+ T cells reactive to peptides covering the mutated regions in the omicron variant decreased compared with the ancestral strain.…”

Section: Discussionmentioning

confidence: 99%

Increased Secondary Attack Rates among the Household Contacts of Patients with the Omicron Variant of the Coronavirus Disease 2019 in Japan

Ogata

Tanaka²,

Tanaka

et al. 2022

IJERPH

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This study investigated the household secondary attack rate (HSAR) of patients with coronavirus disease (COVID-19) during the omicron variant-dominant period. The HSAR of COVID-19 cases during the omicron variant-dominant period (4–20 January 2022) was calculated and compared with the delta variant-dominant period (20 August to 7 November 2021) in Itako, Japan. In Itako, all 47 and 119 samples tested during the omicron and delta variant-dominant periods were negative and positive, respectively, for the L452R mutation. We used a generalized estimating equation regression model. The HSAR was 31.8% (95% confidence interval (CI) 27.7–36.2) for 456 household contacts during the omicron variant-dominant period; it was higher than that during the delta variant-dominant period (25.2%) (adjusted risk ratio [aRR] 1.61, CI 1.13–2.28). During the omicron variant-dominant period, HSAR was lower for the household contacts of completely vaccinated index patients (27.3%) than for contacts of other index patients (41.2%) (vaccine effectiveness for infectee 0.43, 95% CI 0.16–0.62) and was significantly higher for female contacts than for male contacts (36.2% vs. 26.1%; aRR 1.29, 95% CI 1.01–1.65). The HSAR was significantly higher during the omicron variant-dominant period than the delta variant-dominant period. The vaccination of index patients might protect household contacts.

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“… 19 Therefore, a booster shot after 6 months was administered in some countries to increase the neutralizing antibody levels and hopefully protect against Omicron. Although a booster dose, especially after a prolonged interval, was proved to greatly increase the neutralizing antibody level, 17 , 20 – 22 repeated booster administration with the same prototype vaccine may not be a good way to fight against Omicron or future new variants, especially for variants with large changes of antigenicity. Our preliminary data indicated that four doses of the D614G vaccine (14-day interval), were not as good as three doses of D614G plus 1 dose of Beta/Omicron (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses

Zhang

Liang

et al. 2022

Sig Transduct Target Ther

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A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability. To evaluate its antigenicity relationship with other variants, antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants. The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens, and Omicron (BA.1)-elicited sera did not efficiently neutralize the other variants. However, a Beta or Omicron booster, when administered as the 4th dose 3-months after the 3rd dose of any of the variants, could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1. Further analysis with 280 available antigen–antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity. Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.

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Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine

Cited by 31 publications

References 71 publications

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections

Increased Secondary Attack Rates among the Household Contacts of Patients with the Omicron Variant of the Coronavirus Disease 2019 in Japan

Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses

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