Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine

Chalkias, Spyros; Eder, Frank; Essink, Brandon; Khetan, Shishir; Nestorova, Biliana; Feng, Jing; Chen, Xing; Chang, Ying; Zhou, Honghong; Montefiori, David C.; Edwards, Darin K.; Girard, Bethany; Pajón, Rolando; Leav, Brett; Walsh, Stephen R.; Baden, Lindsey R.; Miller, Jacqueline M.; Das, Rituparna

doi:10.21203/rs.3.rs-1555201/v1

Cited by 20 publications

(35 citation statements)

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“…We had previously reported that a bivalent booster vaccine containing the ancestral SARS-CoV-2 and an antigenically-divergent variant can induce antibodies which cross-neutralize and cross-react with multiple variants and consistently elicit higher antibody responses compared to mRNA-1273. 23 mRNA-1273.214 elicited potent neutralizing antibodies responses against the omicron BA.4 and BA.5 subvariants and the increase (fold-rise) in neutralizing antibody titers was consistent with the increase in titers against omicron BA.1, regardless of prior SARS-CoV-2 infection. In addition, the longevity of the neutralizing antibody response is important and we previously observed a more durable response against multiple variants, 6 months after immunization with the beta-containing bivalent vaccine, compared to mRNA-1273.…”

Section: Discussionsupporting

confidence: 54%

“…In addition, the longevity of the neutralizing antibody response is important and we previously observed a more durable response against multiple variants, 6 months after immunization with the beta-containing bivalent vaccine, compared to mRNA-1273. 23 We will continue to monitor the persistence of the antibody responses elicited by mRNA-1273.214 in the ongoing clinical study.…”

Section: Discussionmentioning

confidence: 99%

“…We have also previously evaluated the safety and reactogenicity of another bivalent candidate, mRNA-1273.211, which had similar safety and reactogenicity to the mRNA-1273.214 vaccine, with a reassuring safety profile through 6 months post-vaccination. 23…”

Section: Discussionmentioning

confidence: 99%

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A Bivalent Omicron-containing Booster Vaccine Against Covid-19

Chalkias

Harper

Vrbicky

et al. 2022

Preprint

Self Cite

116

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Background Updated vaccination strategies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are needed. Interim results of the safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster candidate are presented. Methods In this ongoing, phase 2/3 trial, the 50-μg bivalent vaccine mRNA-1273.214 (25-μg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) was compared to the authorized 50-μg mRNA-1273 booster in adults who previously received 2-dose primary series of 100-μg mRNA-1273 and a first booster dose of 50-μg mRNA-1273 at least 3 months prior. Primary objectives were safety and reactogenicity, and immunogenicity of 50-μg mRNA-1273.214 compared with 50-μg mRNA-1273. Immunogenicity data 28 days after the booster dose are presented. Results Four hundred thirty-seven and 377 participants received 50-μg of mRNA-1273.214, or mRNA-1273, respectively. Median time between first and second booster doses of mRNA-1273.214 and mRNA-1273 were similar (136 and 134 days, respectively). In participants with no prior SARS-CoV-2 infection, observed omicron neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after the mRNA-1273.214 and mRNA-1273 booster doses, were 2372.4 (2070.6−2718.2) and 1473.5 (1270.8−1708.4) respectively and the model-based GMT ratio (97.5% confidence interval) was 1.75 (1.49−2.04). All pre-specified non-inferiority (ancestral SARS-CoV-2 with D614G mutation [D614G] GMT ratio; ancestral SARS-CoV-2 [D614G] and omicron seroresponse rates difference) and superiority primary objectives (omicron GMT ratio) for mRNA-1273.214 compared to mRNA-1273 were met. Additionally, mRNA-1273.214 50-μg induced a potent neutralizing antibody response against omicron subvariants BA.4/BA.5 and higher binding antibody responses against alpha, beta, gamma, delta and omicron variants. Safety and reactogenicity profiles were similar and well-tolerated for both vaccines groups. Conclusion The bivalent vaccine mRNA-1273.214 50-μg was well-tolerated and elicited a superior neutralizing antibody response against omicron, compared to mRNA-1273 50-μg, and a non-inferior neutralizing antibody response against the ancestral SARS-CoV-2 (D614G), 28 days after immunization, creating a new tool as we respond to emerging SARS-CoV-2 variants.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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A Bivalent Omicron-containing Booster Vaccine Against Covid-19

Chalkias

Harper

Vrbicky

et al. 2022

Preprint

Self Cite

116

View full text Add to dashboard Cite

show abstract

“…However, a booster dose of the mRNA-1273 vaccine resulted in neutralisation titres against Omicron that were 20-times higher than one month after the second dose of vaccine ( 118 ). Boosting with a bivalent ancestral and Beta (mRNA-1273.211) or Beta and Delta (mRNA-1273.213) vaccine resulted in almost identical neutralisation titres for Omicron as individuals who received a booster with mRNA-1273 alone ( 118 ) ( 137 ). Interestingly, in a recent study that investigated protective immune responses against Omicron in macaques immunized with mRNA-1273 or an mRNA-Omicron vaccine ( 138 ), there was no increased response to Omicron in animals boosted with the Omicron vaccine.…”

Section: Immune Imprinting: a Partnership Of Infection And Vaccine In...mentioning

confidence: 99%

A Complementary Union of SARS-CoV2 Natural and Vaccine Induced Immune Responses

et al. 2022

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Our understanding of the immune responses that follow SARS-CoV-2 infection and vaccination has progressed considerably since the COVID-19 pandemic was first declared on the 11th of March in 2020. Recovery from infection is associated with the development of protective immune responses, although over time these become less effective against new emerging SARS-CoV-2 variants. Consequently, reinfection with SARS-CoV-2 variants is not infrequent and has contributed to the ongoing pandemic. COVID-19 vaccines have had a tremendous impact on reducing infection and particularly the number of deaths associated with SARS-CoV-2 infection. However, waning of vaccine induced immunity plus the emergence of new variants has necessitated the use of boosters to maintain the benefits of vaccination in reducing COVID-19 associated deaths. Boosting is also beneficial for individuals who have recovered from COVID-19 and developed natural immunity, also enhancing responses immune responses to SARS-CoV-2 variants. This review summarizes our understanding of the immune responses that follow SARS-CoV-2 infection and vaccination, the risks of reinfection with emerging variants and the very important protective role vaccine boosting plays in both vaccinated and previously infected individuals.

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“…Bivalent vaccines have become effective tools to respond to the emerging variants. The bivalent vaccine mRNA-1273.211 targeting the prototype and beta strain induced more potent, durable, and wilder humoral responses against key previously circulating VOCs and VOIs, which is superior to mRNA-1273 regarding titers against some VOIs, but also equivalent to peak titers measured after the primary vaccine series against prototype strain [ 25 , 26 ]. Based on the same strategy, the bivalent vaccine mRNA-1273.214 targeting the prototype and Omicron strain has elicited superior neutralizing antibody response against Omicron and non-inferior response against prototype SARS-CoV-2 compared with mRNA-1273 [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

A Heterologous V-01 or Variant-Matched Bivalent V-01D-351 Booster following Primary Series of Inactivated Vaccine Enhances the Neutralizing Capacity against SARS-CoV-2 Delta and Omicron Strains

Zhang

Zhao

et al. 2022

JCM

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Immune escape of emerging SARS-CoV-2 variants of concern (VOCs) and waning immunity over time following the primary series suggest the importance and necessity of booster shot of COVID-19 vaccines. With the aim to preliminarily evaluate the potential of heterologous boosting, we conducted two pilot studies to evaluate the safety and immunogenicity of the V-01 or a bivalent V-01D-351 (targeting Delta and Beta strain) booster after 5–7 months of the primary series of inactivated COVID-9 vaccine (ICV). A total of 77 participants were enrolled, with 20 participants in the V-01D-351 booster study, and 27, 30 participants in the age stratified participants of V-01 booster study. The safety results showed that V-01 or V-01D-351 was safe and well-tolerated as a heterologous booster shot, with overall adverse reactions predominantly being absent or mild in severity. The immunogenicity results showed that the heterologous prime–boost immunization with V-01 or bivalent V-01D-351 booster induced stronger humoral immune response as compared with the homologous booster with ICV. In particular, V-01D-351 booster showed the highest pseudovirus neutralizing antibody titers against prototype SARS-CoV-2, Delta and Omicron BA.1 strains at day 14 post boosting, with GMTs 22.7, 18.3, 14.3 times higher than ICV booster, 6.2, 6.1, 3.8 times higher than V-01 booster (10 μg), and 5.2, 3.8, 3.5 times higher than V-01 booster (25 μg), respectively. The heterologous V-01 booster also achieved a favorable safety and immunogenicity profile in older participants. Our study has provided evidence for a flexible roll-out of heterologous boosters and referential approaches for variant-specific vaccine boosters, with rationally conserved but diversified epitopes relative to primary series, to build herd immunity against the ongoing pandemic.

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Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine

Cited by 20 publications

References 0 publications

A Bivalent Omicron-containing Booster Vaccine Against Covid-19

A Bivalent Omicron-containing Booster Vaccine Against Covid-19

A Complementary Union of SARS-CoV2 Natural and Vaccine Induced Immune Responses

A Heterologous V-01 or Variant-Matched Bivalent V-01D-351 Booster following Primary Series of Inactivated Vaccine Enhances the Neutralizing Capacity against SARS-CoV-2 Delta and Omicron Strains

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