Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose

Lustig, Yaniv; Gonen, Tal; Meltzer, Lilac; Gilboa, Mayan; Indenbaum, Victoria; Cohen, Carmit; Amit, Sharon; Jaber, Hanaa; Doolman, Ram; Asraf, Keren; Rubin, Carmit; Fluss, Ronen; Mendelson, Ella; Freedman, Laurence S.; Regev‐Yochay, Gili; Kreiss, Yitshak

doi:10.1038/s41590-022-01212-3

Cited by 84 publications

(83 citation statements)

References 21 publications

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“…In contrast, in the present study of the booster dose for the same cohort, male sex and age showed positive correlations with the fold change in IgG(S-RBD) titers, reaching comparable levels in the IgG(S-RBD) titers by sex and age. Other studies have also shown that the specific IgG titers after the BNT162b2 booster were comparable for sex and age [22,23]. The mechanism for the difference in the immunogenicity of a BNT162b2 vaccine by sex and age between the second and booster doses is unclear, but the booster vaccination would drive antibody productions, especially in the populations with relatively weak responses to the primary series.…”

Section: Discussionmentioning

confidence: 99%

Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication

Tani

Ikematsu

Goto

et al. 2022

Preprint

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Background: A SARS-CoV-2 mRNA vaccine booster elicits sufficient antibody responses that protect against COVID-19, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 two-dose primary series. Spike-specific IgG titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for seven days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (beta=0.305, p<0.001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk: 3.97 [95% confidence interval: 2.48-6.35]); however, the IgG titers after the booster dose were not affected by fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions would not interfere with the elevation of specific IgG titers.

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Section: Discussionmentioning

confidence: 99%

Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication

Tani

Ikematsu

Goto

et al. 2022

Preprint

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“…The observation that average humoral responses to three-dose vaccination failed to protect against Omicron BA.1 infection is consistent with the extremely high rates of community transmission observed in many regions during the recent Omicron-driven pandemic waves. Given that third doses substantially boost humoral responses in individuals of all ages (29)(30)(31)(32), the risk of Omicron infection is likely to be higher among individuals who have received fewer than three doses (18,33) and is likely to increase with time following vaccination due to natural declines in antibody responses (26,(34)(35)(36)(37). Additional studies are needed to assess these factors.…”

Section: Discussionmentioning

confidence: 99%

Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

Lapointe

Mwimanzi

Cheung

et al. 2022

Preprint

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SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have documented serial Omicron infections. We characterized SARS-CoV-2 humoral responses in a healthy young person who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to those of 124 COVID-19 naive vaccinees. One month after the second and third vaccine doses, the participant’s wild-type and BA.1-specific IgG, ACE2 competition and virus neutralization activities were average for a COVID-19 naive triple-vaccinated individual. BA.1 infection boosted the participant’s responses to the cohort ≥95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Moreover, reinfection increased BA.1 and BA.2-specific responses only modestly. Results illustrate the risk of Omicron infection in fully vaccinated individuals and highlight the importance of personal and public health measures as vaccine-induced immune responses wane.

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“…However, acquired immunity after vaccination does not persist at high levels, but begins to wane, and breakthrough infections frequently develop even in people who have received the requisite two dose series of BNT162b2 [2,3]. Although new variants of concern that escape the immune system are another potential cause of lower vaccine effectiveness, serial reductions of both spike IgG and neutralizing antibodies have been reported in various publications [4][5][6][7][8][9][10][11][12][13][14][15][16], and these findings support a third vaccine dose to boost antibody production, to control resurgent COVID-19 [17][18][19][20][21][22]. Due to limited vaccine supply, an individualized booster vaccine schedule is recommended to conserve vaccine doses and to prioritize them to high-risk patients or developing countries.…”

Section: Introductionmentioning

confidence: 89%

Temporal changes in spike IgG levels after two doses of BNT162b2 vaccine in Japanese healthcare workers: Do spike IgG levels at 3 months predict levels 6 or 8 months after vaccination?

et al. 2022

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Background Accurate timing of BNT162b2 boosters to prevent breakthrough infections of coronavirus disease 2019 (COVID-19) requires reliable estimates of immune status. We hypothesized that spike IgG levels at 3 months after two doses of the BNT162b2 vaccine might predict subsequent spike IgG levels. Methods and results Spike IgG levels were tested at 3, 6, and 8 months after the second dose of the BNT162b2 vaccine in 251 Japanese health care workers (median age: 39 years, female: 187). The median level of spike IgG was 2,882 AU/mL at 3 months. This decreased to 875 AU/mL at 6 months and 579 AU/mL at 8 months. There were good correlations of log-transformed spike IgG levels between 3 and 6 months (r = 0.86) and between 3 and 8 months (r = 0.82). The correlation further improved after excluding three subjects who had possible COVID-19 infections (r = 0.91, r = 0.86). Log-transformed spike IgG levels at 6 or 8 months yields the following equation: log spike IgG at 6 (8) months = 0.92 (0.86) X log spike IgG at 3 months– 0.23 (0.18). Predicted spike IgG at 6 months of ≥ 300 or < 300 AU/mL had 98% sensitivity, 47% specificity, and 94% accuracy for discriminating subjects whose actual spike IgG titers at 6 months were above or below 300 AU/mL. Corresponding values of predicted spike IgG at 8 months were 97%, 70%, and 93%, respectively. Conclusions We conclude that predictive formulae using spike IgG levels at 3 months after two-dose vaccination with BNT162b2 reliably estimate subsequent spike IgG levels up to 8 months and provide useful information in terms of vaccination booster timing.

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Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose

Cited by 84 publications

References 21 publications

Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication

Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication

Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

Temporal changes in spike IgG levels after two doses of BNT162b2 vaccine in Japanese healthcare workers: Do spike IgG levels at 3 months predict levels 6 or 8 months after vaccination?

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