Immunogenicity of a third dose of BNT162b2 to ancestral SARS-CoV-2 &amp; Omicron variant in adults who received two doses of inactivated vaccine

Leung, Nancy; Cheng, Samuel; Martín-Sánchez, Mario; Au, Niki Y. M.; Ng, Yvonne Ying Ru; Luk, Leo L. H.; Chan, Ka‐Kui; Li, John K. C.; Leung, Yonna W. Y.; Tsang, Leo C. H.; Chaothai, Sara; Kwan, Kelvin K. H.; Ip, Dennis Kai Ming; Poon, Leo L M; Leung, Gabriel M.; Peiris, Malik; Cowling, Benjamin J.

doi:10.1101/2022.01.20.22269586

Cited by 4 publications

(10 citation statements)

References 35 publications

(67 reference statements)

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“…When using high-dose aerosolized Ad5-nCoV as a booster dose, the seropositivity was similar to that in the low-dose aerosolized Ad5-nCoV group. Consistent with previous studies [25,26], our study suggested that although omicron variant evaded NAb responses elicited by the homologous CoronaVac boost regimen, the heterologous boost regimen may provide protection against omicron variant.…”

Section: Discussionsupporting

confidence: 92%

Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously

Jin

Tang

et al. 2022

Preprint

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Background: Heterologous orally administered adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in individuals who were primed with two-dose CoronaVac (an inactivated SARS-CoV-2 vaccine, by Sinovac) previously, has been reported to be safe and highly immunogenic within 28 days post-boosting. However, antibody persistence and safety up to 6 months of this regimen are not been reported yet. Methods: This is a randomized, open label, single-center trial on safety and immunogenicity of heterologous boost immunization with an orally administered aerosolised Ad5-nCoV vs. homologous boost immunization with CoronaVac after two-dose priming with CoronaVac in Chinese adults aged 18 years and older (NCT05043259). We followed the participants in this trial, including 140 in the low-dose aerosolised Ad5-nCoV group, 139 in the high-dose aerosolised Ad5-nCoV group, and 140 in the CoronaVac group for 6 months. Neutralising antibodies (NAbs) against live wild-type SARS-CoV-2 virus and omicron variant, and receptor-binding domain (RBD)-specific IgG antibodies were detected in serum samples collected at 28 days, 3 months, and 6 months after the booster dose. Serious adverse events (SAEs) were documented till month 6. Results: The low-dose and high-dose heterologous boost immunisation groups had NAb GMTs against live wild-type SARS-CoV-2 of 1937.3 [95% CI 1466.9, 2558.4] and 1350.8 [95% CI 952.6, 1915.3], which were 26.4 folds and 18.4 folds higher than that the CoronaVac group did (73.5 [95%CI 52.3, 103.3]) at 28 days. The low-dose and high-dose heterologous boost immunisation groups had NAb GMTs against live wild-type SARS-CoV-2 of 530.1 (95% CI 412.5, 681.1) and 457.6 (95%CI 349.4, 599.2), which were 26.0 folds and 22.4 folds higher than that the CoronaVac group did (20.4 [95%CI 14.3, 29.1]) at 3 months, respectively. At 6 months, the low-dose and high-dose heterologous booster groups had NAb GMTs against live wild-type SARS-CoV-2 of 312.9 (95%CI 237.7, 411.8) and 251.1 (95%CI 178.2, 354.0), which were 30.1 folds and 24.1 folds higher than the CoronaVac group did (10.4 [95%CI 7.8, 14.0]), respectively. Additionally, the low-dose and high-dose heterologous booster groups had NAb GMTs against live omicron variant of 52.0 (95%CI 37.2, 72.6) and 23.1 (95%CI 15.7, 33.9) at 28 days, 27.9 (95% CI 18.8, 41.3) and 23.3 (95%CI 16.2, 33.3) at 3 months, 16.0 (95%CI 10.9, 23.5) and 12.0 (95%CI 8.5, 16.8) at 6 months, respectively. However, nearly all participants had no detectable NAbs for omicron variant in the CoronaVac group at either 28 days, 3 months, or 6 months. No vaccine-related SAEs were observed. Conclusions: These data suggested that heterologous aerosolised Ad5-nCoV following two-dose CoronaVac priming was safe and persistently more immunogenic than three-dose CoronaVac, although immune responses waned over time.

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Section: Discussionsupporting

confidence: 92%

Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously

Jin

Tang

et al. 2022

Preprint

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“…We conducted an open-label single-arm trial to measure the antibody responses to a third dose of BNT162b2 in adults ≥30 years old who previously received two doses of an inactivated COVID-19 vaccine with the second inactivated vaccine dose at least 90 days prior to enrolment [8]. The BNT162b2 vaccine and the inactivated vaccine CoronaVac (Sinovac) were both approved for use in Hong Kong in early 2021, while an alternative inactivated vaccine BIBP (Sinopharm) has been available since early 2021 in mainland China and some other countries.…”

Section: Methodsmentioning

confidence: 99%

“…We enrolled participants from October through December 2021. Participants were not eligible if they had received any other COVID-19 vaccination apart from the two doses of inactivated vaccination, if they had a history of laboratory-confirmed COVID-19 infection, if they met a contraindication for BNT162b2, were receiving immuno-modulatory 5 medications, or were females who were pregnant or intending to become pregnant in the coming 3 months [8].…”

Section: Methodsmentioning

confidence: 99%

“…In recipients of two initial doses of inactivated COVID-19 vaccines, we and others have shown that a third "booster" dose of BNT162b2 (BioNTech/Pfizer/Fosun Pharma) confers a very strong antibody response both against the ancestral strain and the Omicron variant [8][9][10]. Here, we explore the persistence of antibody titers up to 6 months after a third dose of BNT162b2 in this regimen.…”

Section: Introductionmentioning

confidence: 99%

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Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine

Cowling

Cheng

Martín-Sánchez

et al. 2022

Preprint

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IntroductionThird doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses.MethodsWe administered BNT162b2 as a third dose to adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2.ResultsWe administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity.ConclusionsWhile antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.

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“…5 While some booster campaigns have encouraged individuals to receive a homologous third dose, a third/booster dose with a different vaccine platform, i.e., heterologous vaccination, could be more feasible in some locations. [6][7][8] There is also a possibility that combining vaccine doses using different vaccine platforms by heterologous prime-boost strategies might enhance the immune response. 9 Heterologous vaccination has been investigated by a number of clinical trials with mixed results depending on the initial platform and sequence of vaccination.…”

Section: Introductionmentioning

confidence: 99%

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

Leung

Cheng²,

Cohen

et al. 2022

Preprint

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Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac ("CC-C", n=101) or BNT162b2 ("CC-B", n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac ("BB-C", n=118) or BNT162b2 ("BB-B", n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Third doses significantly increased neutralising PRNT50 antibody titers against ancestral virus and Omicron BA.1 variant in all four study arms, and against Omicron BA.2 in all arms except CC-C, with statistically significant improvements for recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. Boosting of CD4+ T cells only occurred in CoronaVac-primed arms, but we did not identify overall differences between vaccine groups in CD4+ and CD8+ T cell responses. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

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Immunogenicity of a third dose of BNT162b2 to ancestral SARS-CoV-2 & Omicron variant in adults who received two doses of inactivated vaccine

Cited by 4 publications

References 35 publications

Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously

Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously

Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

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