Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages

Richardson, Simone I.; Lambson, Bronwen E.; Kgagudi, Prudence; Mzindle, Nonkululeko; Kaldine, Haajira; Crowther, Carol; Gray, Glenda; Bekker, Linda‐Gail; Koen, Anthonet; Fairlie, Lee; Fouche, Leon; Bhorat, Qasim; Dheda, Keertan; Tameris, Michèle; Masilela, Mduduzi; Hoosain, Zaheer; Singh, Nishanta; Hanley, Sherika; Archary, Moherndran; Louw, Cheryl; Grobbelaar, Coert; Lalloo, Umesh; Joseph, Natasha; Kruger, Gertruida; Bennett, Chijioke; Glenn, Gregory M.; Madhi, Shabir А.; Moore, Penny L.

doi:10.1101/2022.07.14.500148

Cited by 17 publications

(19 citation statements)

References 14 publications

(25 reference statements)

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“…High anti-WT/anti-BA.1 pVNT 50 titers of 12,778/2,352 for UB-612 were first observed in our Phase-1 booster vaccination study (43) ( Supplemental Figure 4B ). As to “anti-WT vs. anti-BA.1 vs. anti-BA.2,” UB-612 booster exhibits a combined pVNT 50 value profile of 6254-12,778 vs. 1196-2325 vs. 985-1819” ( Table 2A ), which are comparable to the respective counterparts reported for NVX-CoV2373 (44), mRNA-1273 (7), BNT162b2 (2), yet far greater than for MVC-COV1901 (45), CoronaVac (6), AZD1222 (2), and BBIP-CorV (46). All listed anti-BA.1/BA.2 pVNT 50 values account for approximately a ∼3.7- to 20-fold reduction; and, relative to anti-BA.1/-BA.2, the overall anti-BA.5 pVNT 50 is estimated to be within 2- to 3-fold reduction.…”

Section: Discussionsupporting

confidence: 56%

“…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%

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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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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 95%

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

View full text Add to dashboard Cite

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“…Consistent with the anti-RBD Ig and IgG responses observed in this study, the booster dose elicited a high immune response and neutralizing activity against wild type and omicron BA.2 variants of SARS-CoV-2. However, neutralizing antibodies against the omicron variant were slightly lower than that toward the prototype variant (Bhiman et al, 2022). Several mutations in the RBD could alter the binding affinity of antibodies produced from wild type vaccines (Cao et al, 2022).…”

Section: Discussionmentioning

confidence: 81%

“…The protein subunit vaccine, which derives from a more traditional technology, may appear to have lower side effects in this setting, although this remains to be seen. Moreover, protein subunit vaccines present additional benefits than the viral vector and mRNA vaccines because as they overcome the limitations due to storage conditions and is easier to ship to rural/remote areas (Bhiman et al, 2022; Fiolet et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (Covovax™) after homologous and heterologous two-dose regimens

Kanokudom

Chansaenroj²,

Suntronwong³

et al. 2022

Preprint

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Objective: To report the safety and immunogenicity profile of a protein subunit vaccine (CovovaxTM) given as a third (booster) dose to individuals primed with different primary vaccine regimens. Methods: Individuals primed with two doses of COVID-19 vaccines for at least 3 months were enrolled and assigned to five groups according to their primary vaccine regimens: CoronaVac, BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell response. Results: Overall, 215 individuals were enrolled and boosted with the CovovaxTM vaccine. The reactogenicity achieved was mild-to-moderate. Most participants elicited a high level of binding and neutralizing antibody responses against wild type and omicron variants following the booster dose. The 197 participants were classified by anti-N IgG. Of these, 141/197 (71.6%) were a seronegative population, and neutralizing activity and IFN-γ release were further monitored. A booster dose could elicit neutralizing activity to wild type and omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The CovovaxTM vaccine could elicit a cell-mediated immune response. Conclusion: The protein subunit vaccine (CovovaxTM) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles. Keywords: Severe acute respiratory virus 2 (SARS-CoV-2); Omicron; side effect; CovovaxTM; Novavax; booster dose

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“…3,4 Although studies evaluating its efficacy against Omicron are ongoing, 1 study reported that 3 doses of NVX-CoV2373 induced neutralizing antibody titres against Omicron BA.1 and BA.4, similar to 3 doses of mRNA vaccine. 5 Boosting with NVX-CoV2373 resulted in lower antibody titres than boosting with an mRNA vaccine. 2…”

Section: Nvx-cov2373 Is Efficaciousmentioning

confidence: 99%

NVX-CoV2373, a protein-based vaccine against SARS-CoV-2 infection

Vohra-Miller

Schwartz

2022

CMAJ

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NVX-CoV2373 (marketed as Nuvaxovid) is a protein-based vaccine against SARS-CoV-2, approved in Canada for adults unable or unwilling to receive an mRNA vaccine Protein-based vaccines have a long history of use that may make them more acceptable to patients who are hesitant to receive mRNA vaccination. 1 NVX-CoV2373 consists of a recombinant spike protein subunit plus adjuvant. It may also be considered for people who are allergic to components of mRNA vaccines (e.g., polyethylene glycol). 2 2 NVX-CoV2373 can be used in a primary series of vaccination NVX-CoV2373 can be administered in a 2-dose primary series or as a heterologous primary series with another approved vaccine against SARS-CoV-2. Doses should be separated by 8 weeks to maximize immune response. 2 3 NVX-CoV2373 may be offered as a boosterAlthough not approved by Health Canada for this indication, the National Advisory Committee on Immunizations recommends NVX-CoV2373 as a booster 6 months after any primary series. 2

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Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages

Cited by 17 publications

References 14 publications

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

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

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (Covovax™) after homologous and heterologous two-dose regimens

NVX-CoV2373, a protein-based vaccine against SARS-CoV-2 infection

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