Effects of a Prolonged Booster Interval on Neutralization of Omicron Variant

Zhao, Xin; Li, Dedong; Ruan, Wenjing; Chen, Zhihai; Zhang, Rong; Zheng, Anqi; Qiao, Shitong; Zheng, Xinlei; Zhao, Yang; Dai, Lianpan; Han, Pengcheng; Gao, Lidong

doi:10.1056/nejmc2119426

Cited by 95 publications

(99 citation statements)

References 4 publications

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“…Thus, the effectiveness of a vaccine booster for the Omicron variant has become a worldwide concern. The effectiveness of the booster against the Omicron variant has been reported mainly in countries and regions where the booster was previously implemented [8][9][10][11][12]. However, there is little evidence of the efficacy of booster vaccination against the Omicron variant in Japan because the booster was started after the appearance of the variant.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population

Kawasuji¹,

Morinaga

Tani

et al. 2022

Preprint

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Introduction The vaccine against SARS–CoV–2 provides humoral immunity to fight COVID-19; however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity; however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID–19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster. Methods Serum samples were obtained from healthcare workers (20−69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti–SARS–CoV–2 antibody level was measured, and neutralization against the wild–type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster–related events were collected using questionnaires. Results The median anti–SARS–CoV–2 antibody was >30.9–fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0−1068.0 U/mL]; 2wA3D, 21927 U/mL [IQR: 15321.0−>25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild–type–, Delta–, and Omicron–derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti–SARS–CoV–2 antibody levels were significantly elevated in individuals with fever ≥ 37.5 °C, general fatigue, and myalgia, local swelling, and local hardness. Conclusion The booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.

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Section: Introductionmentioning

confidence: 99%

Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population

Kawasuji¹,

Morinaga

Tani

et al. 2022

Preprint

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“…By giving a fourth BNT162b2 booster to poor immune responders, anti-RBD IgG increased to a lesser extent compared to the third booster dose (7 fold versus 15 fold), possibly due to the short interval between the third and fourth booster 10 .…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of the third and fourth BNT162b2 mRNA COVID-19 boosters and factors associated with immune response in systemic lupus erythematosus and rheumatoid arthritis patients

Assawasaksakul

Sathitratanacheewin

Vichaiwattana

et al. 2022

Preprint

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Objectives: To evaluate the safety and immunogenicity of third and fourth BNT162b2 boosters in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. Methods: SLE and RA patients aged 18-65 years who completed a series of inactivated, adenoviral vector, or heterogenous adenoviral vector/mRNA vaccines for at least 28 days were enrolled. Immunogenicity assessment was done before and day 15 after each booster vaccination. The third BNT162b2 booster was administered on day 1. Patients with suboptimal humoral response to the third booster dose (anti-receptor binding domain (RBD) IgG on day 15 < 2,360 BAU/mL) were given a fourth BNT162b2 booster on day 22. Results: Seventy one SLE and 29 RA patients were enrolled. The third booster raised anti-RBD IgG by 15 fold and patients with positive neutralizing activity against the Omicron variant increased from 0% to 42%. Patients with positive cellular immune response also increased from 55% to 94%. High immunosuppressive load and initial inactivated vaccine were associated with lower anti-RBD IgG titer. Fifty four patients had suboptimal humoral responses to the third booster and 28 received a fourth booster dose. Although anti-RBD IgG increased further by 7 fold, no significant change in neutralizing activity against the Omicron variant was observed. There were 2 severe SLE flares that occurred shortly after the fourth booster dose. Conclusions: The third BNT162b2 booster significantly improved humoral and cellular immunogenicity in SLE and RA patients. The benefit of a short interval fourth booster in patients with suboptimal humoral response was unclear.

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“…Additionally, two-dose schedule with D0-M5 and D0-M6 induced comparable antibody level comparable with that elicited by three doses of heterologous immunization with D0-D28-M5 and D0-D56-M6 schedules. Zhao et al (24) also showed that prolonged-interval ZF2001 (receiving three doses of ZF2001 at interval of month 0, 1 and 4, M0-M1-M4) induced higher binding and neutralizing antibodies than the short-interval ZF2001 (M0-M1-M2), including against SARS-CoV-2 prototype strain and variants of concern such as Delta and Omicron. These findings support the use of a prolonged booster interval to elicit stronger immune responses in persons who had previously received prime immunization of COVID-19 vaccine.…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): a randomized, observer-blinded, placebo-controlled trial

Jin

Guo

Chen

et al. 2022

Preprint

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Background Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001). Methods and Findings We did a randomized, observer-blinded, placebo-controlled trial in healthy adults previously received one dose of Convidecia. Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. For both regimens, all participants received the 2nd injection with ZF2001 at 4 months after a dose of ZF2001 or TIV, with three-dose schedules of Convidecia/Convidecia/ZF2001 at day 0, day 28 and month 5 (referred to as CV/ZF/ZF (D0-D28-M5)) and CV/ZF/ZF (D0-D56-M6), and two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6). The primary outcome was the geometric mean titer (GMT) of the neutralizing antibodies against live SARS-CoV-2 virus 14 days after each boost vaccination. The safety outcome was 7-day reactogenicity, measured as solicited local or systemic adverse reactions after each vaccination. Between April 7, 2021, and May 6, 2021, 120 participants were enrolled, among whom 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 28-day interval, and 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 56-day interval. 113 (94.2%) participants received the 2nd injection with ZF2001 4 months after a dose of ZF2001 or TIV. A total of 26 participants (21.7%) reported solicited adverse events within 7 days post boost vaccinations, and all the reported adverse reactions were mild . Among participants receiving ZF001 as second dose, the GMTs of neutralizing antibodies increased to 58.4 IU/ml (42.8-79.8) in 0-28 regimen, and to 80.8 IU/ml (53.1-122.9) in 0-56 regimen at 14 days post first boost dose. The GMTs of neutralizing antibodies increased to 334.9 IU/ml (95% CI 230.4, 486.9) in C/Z/Z (D0-D28-M5) regimen, and 441.2 IU/ml (260.8, 746.4) in C/Z/Z (D0-D56-M6) regimen at 14 days after the third dose. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced comparable antibody level comparable with that elicited by three-dose schedules, with the GMTs of 282.9 IU/ml (142.5, 561.8) and 293.9 IU/ml (137.6, 627.9), respectively. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron. Conclusions Heterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating viral vectored vaccines and recombinant protein vaccine. Trial Registration ClinicalTrial.gov NCT04833101

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Effects of a Prolonged Booster Interval on Neutralization of Omicron Variant

Cited by 95 publications

References 4 publications

Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population

Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population

Immunogenicity of the third and fourth BNT162b2 mRNA COVID-19 boosters and factors associated with immune response in systemic lupus erythematosus and rheumatoid arthritis patients

Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): a randomized, observer-blinded, placebo-controlled trial

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