Rapid Decline in Vaccine-Boosted Neutralizing Antibodies Against SARS-CoV-2 Omicron Variant

Lyke, Kirsten E.; Atmar, Robert L.; Islas, Clara Domínguez; Posavad, Christine M.; Szydlo, Daniel; PaulChourdhury, Rahul; Deming, Meagan E.; Eaton, Amanda; Jackson, Lisa A.; Branche, Angela  Ramon; Sahly, Hana M. El; Rostad, Christina A.; Martin, Judith M.; Johnston, Christine; Rupp, Richard; Mulligan, Mark J.; Brady, Rebecca C.; Frenck, Robert W.; Bäcker, Martín; Kottkamp, Angélica; Babu, Tara M; Rajakumar, Kumaravel; Edupuganti, Srilatha; Dobrzynski, David; Coler, Rhea N.; Archer, Janet I.; Crandon, Sonja; Zemanek, Jillian A.; Brown, Elizabeth R.; Neuzil, Kathleen M.; Stephens, David S.; Post, Diane J.; Nayak, Seema; Suthar, Mehul S.; Beigel, John H; Montefiori, David C.

doi:10.2139/ssrn.4061187

Cited by 26 publications

(45 citation statements)

References 4 publications

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“…Resistance to antiviral humoral immunity can be mainly determined by substitutions in the spike (S) protein. For instance, Omicron BA.1 (Cao et al, 2021;Cele et al, 2021;Dejnirattisai et al, 2022;Garcia-Beltran et al, 2021;Liu et al, 2021;Meng et al, 2022;Planas et al, 2021;Takashita et al, 2022a;VanBlargan et al, 2022) , BA.2 (Bruel et al, 2022;Takashita et al, 2022b;Yamasoba et al, 2022c), andBA.5 (Arora et al, 2022;Cao et al, 2022;Gruell et al, 2022;Hachmann et al, 2022;Khan et al, 2022;Kimura et al, 2022c;Lyke et al, 2022;Qu et al, 2022;Tuekprakhon et al, 2022;Wang et al, 2022;Yamasoba et al, 2022c) exhibit profound resistance to neutralizing antibodies induced by vaccination, natural SARS-CoV-2 infection, and therapeutic monoclonal antibodies. Particularly, newly spreading SARS-CoV-2 variants tend to be resistant to the humoral immunity induced by the infection with prior variant; for instance, BA.2 is resistant to BA.1 breakthrough infection sera (Qu et al, 2022;Tuekprakhon et al, 2022;Yamasoba et al, 2022b), and BA.5 is resistant to BA.2 breakthrough infection sera (Hachmann et al, 2022;Kimura et al, 2022c;Wang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75

Saito

Tamura

Zahradník

et al. 2022

Preprint

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SARS-CoV-2 Omicron BA.2.75 emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically different from BA.5, the currently predominant BA.2 descendant. Here, we showed that the effective reproduction number of BA.2.75 is greater than that of BA.5. While the sensitivity of BA.2.75 to vaccination- and BA.1/2 breakthrough infection-induced humoral immunity was comparable to that of BA.2, the immunogenicity of BA.2.75 was different from that of BA.2 and BA.5. Three clinically-available antiviral drugs were effective against BA.2.75. BA.2.75 spike exhibited a profound higher affinity to human ACE2 than BA.2 and BA.5 spikes. The fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were comparable to those of BA.5 but were greater than those of BA.2. Our multiscale investigations suggest that BA.2.75 acquired virological properties independently of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.

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Section: Introductionmentioning

confidence: 99%

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75

Saito

Tamura

Zahradník

et al. 2022

Preprint

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“…While the rank order of pVNT 50 against Omicrons BA.1/BA.2/BA.5 trends downward ( Figure 3A ) and UB-612 booster combats the most contagious BA.5 with a 13-fold reduction relative to anti-WT titer, its anti-BA.5 pVNT 50 titer of 854 represents a substantially high neutralizing activity. In contrast, an anti-BA.5 pVNT 50 titer of 582 was reported for NVX-CoV2373 (44), 378 for mRNA-1273 (7), 360 for BNT162b2 (2, 3), 75 for CoronaVac (6) and 43 for AZD1222 (2) ( Table 2A ). All available anti-BA.5 pVNT 50 values account for approximately an 8.4- to 21-fold reduction.…”

Section: Discussionmentioning

confidence: 95%

“…Secondly, on the level of live virus-neutralizing titer (VNT 50 /ID 50 /FRNT 50 ) against Omicron BA.1 and BA.2 ( Table 2B ), UB-612 booster excels over other vaccine platforms. UB-612 booster elicits an anti-WT/anti-BA.1 titer profile of 6,159/670 (47), in contrast with 1699/81.0 for mRNA-1273 (7), 640-673/46.2-106 for BNT162b2 (7, 29), and 723/57 for AZD1222 (48). UB-612’s anti-BA.1 titer of 670 far exceeds other vaccines by ∼6- to 12-fold higher.…”

Section: Discussionmentioning

confidence: 99%

“…The SARS-CoV-2 Omicron lineage has swept the globe with a rapid succession of dominating subvariants from BA.1, BA.2 and to the current BA.5 that takes up more than 90% infection cases with overriding edges in transmissibility and neutralizing antibody escape (1)(2)(3)(4)(5)(6)(7). Relative to Delta variant, Omicron BA.1 does not require fusion co-receptor TMPRSS2 for cell entry; instead, cells engulf it and land intracellularly through endosomes (8,9).…”

Section: Introductionmentioning

confidence: 99%

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UB-612 Multitope Vaccine Targeting SARS-CoV-2 Spike and Non-Spike Proteins Provides Broad and Durable Immune Responses

Wang

Peng

Kuo

et al. 2022

Preprint

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The SARS-CoV-2 non-Spike (S) structural protein targets of nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, have been grossly overlooked since the inception of COVID vaccine development. To pursue a universal (pan-sarbecovirus) vaccine against ever-emergent future mutants, we explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved rationally designed promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation of infection-free participants (aged 18-85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6-8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). Booster vaccination is safe and well tolerated without SAEs. By recognition against epitopes on Spike (S1-RBD and S2) and non-Spike (N and M) structure proteins, UB-612 provides potent, broad and long-lasting B-cell and T-cell memory immunity and offers a potential as a universal vaccine to fend off Omicrons and new VoCs.SIGNIFICANCE STATEMENTThe Omicron has swept the globe with a rapid succession of dominating sublineages from BA.1, BA.2, to the current BA.5 with increasing infectivity and antibody evasion. Concerningly, the non-Spike structure proteins that promote T-cell immunity are grossly overlooked in vaccine development. Looking beyond short-interval booster jabs and omicron-updated vaccines, a pragmatic approach to curbing ever-emergent new mutants would be “universal (pan-Sarbecovirus) vaccines” targeting conserved nonmutable epitopes on coronavirus. UB-612, a multitope-vaccine armed with Spike (S1-RBD and S2) and non-Spike targets (Nucleocapsid N and Membrane M), allows booster vaccination to elicit potent, broadly-recognizing, durable B- and T-cell memory immunity. Sequence-conserved epitope peptides were rationally-designed from S2, N and M proteins to synergistically enhance memory helper and cytotoxic T-cell immunity and B-cell immunity.

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“…As of August 2022, WHO has updated its SAR-CoV-2 list of variants of concern (VoC) to consist solely of the Omicron variant and its subvariants [3]. The implication of the Omicron variants as the circulating VoC is that primary series and even booster vaccination with currently available vaccines have shown to perform poorly against the current circulating Omicron variant and its subvariants in general, including the BA.2 and BA.4/BA.5 subvariants [4, 5]. Various Omicron variant-based vaccines have been developed or are in development, including a monovalent mRNA vaccine based on the Omicron variant by Pfizer/BNT is in the midst of a phase 2/3 clinical trial that claimed to have demonstrated effective neutralisation against the BA.1 subvariant and to a lesser extent, the BA.4 and BA.5 subvariants [6].…”

Section: Introductionmentioning

confidence: 99%

A Phase I, Prospective, Randomized, Open-labeled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Booster Dose with MVC-COV1901 or MVC-COV1901(Beta) SARS-CoV-2 Vaccine in Adults

Lien

Liu

Wang

et al. 2022

Preprint

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BackgroundThe use of variant-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as a booster is being evaluated to overcome reduced neutralisation of variants induced by the original SARS-CoV-2 vaccine and waning protection over time.MethodsThis is a phase one, prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901 or its Beta version, MVC-COV1901-Beta. One-hundred and seven participants aged ≥18 and <55 years, who received two or three prior doses of MVC-COV1901 vaccines, were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg or 25 mcg of MVC-COV1901-Beta in 1:1:1 ratio. The primary endpoints were the incidences of adverse events and immunogenicity of the booster dose from Visit 2 (the day of the booster) to Visit 5 (four weeks after the booster). Cellular immunity was also investigated with memory B cell (MBC) and T cell assays.FindingsAdverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 exhibited numerically higher levels of neutralising antibodies against SARS-CoV-2 or Beta variant than participants with three prior doses of MVC-COV1901 regardless of the type of booster used. However, compared to 15 mcg of MVC-COV1901, 25 mcg of MVC-COV1901-Beta significantly improved neutralising antibody titre against Beta variant and BA.4/BA.5 Omicron variant pseudoviruses. The booster dose also significantly increased the proportion of spike-specific MBCs, including those of Beta and Omicron variants.InterpretationMVC-COV1901-Beta can be effectively used as a booster dose against SARS-CoV-2, including the circulating BA.4/BA.5 Omicron variant.FundingMedigen Vaccine Biologics Corporation

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Rapid Decline in Vaccine-Boosted Neutralizing Antibodies Against SARS-CoV-2 Omicron Variant

Cited by 26 publications

References 4 publications

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75

UB-612 Multitope Vaccine Targeting SARS-CoV-2 Spike and Non-Spike Proteins Provides Broad and Durable Immune Responses

A Phase I, Prospective, Randomized, Open-labeled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Booster Dose with MVC-COV1901 or MVC-COV1901(Beta) SARS-CoV-2 Vaccine in Adults

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