A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and <i>Neisseria meningitidis</i> outer membrane vesicles

Santana, Darielys; Pérez-Nicado, Rocmira; Climent-Ruíz, Yanet; Noda, Laura Marta Marta Rodríguez; Ramírez, Belinda Sánchez; Pérez-Rodríguez, Sonia; Rodriguez, Meybi; Regalado, Claudia Labrada; Hernández, Tays; Diaz, Marianniz; Orosa, Ivette; Ramírez, Ubel; Oliva, Reynaldo; Garrido, Raine; Cardoso, Félix; Landys, Mario; Martínez, Roselyn; González, Humberto; Hernández, Teresa; Ochoa-Azze, Rolando Felipe; Pérez, José Luís; Enriquez, Juliet; Gonzalez, Nibaldo; Infante, Yenicet; Espinosa, Luis Ariel; Ramos, Yassel; González, Luís Javier Durán; Valenzuela, Carmen; Casadesús, Ana Victoria; Fernández, B Díaz; Rojas, Gertrudis; Pérez-Massón, Beatriz; Tundidor, Yaima; Bermúdez, Ernesto Cañarte; Plasencia, Claudia  A.; Boggiano, Tammy; Ojito, Eduardo; Chiodo, Fabrizio; Fernández, Sonsire; Paquet, Françoise; Cheng, Fang; Chen, Guang-Wu; Rivera, Daniel G.; Valdés, Yolanda; Dagmar, Garcia-Rivera; Bencomo, Vicente Vérez

doi:10.1039/d1cb00200g

Cited by 16 publications

(20 citation statements)

References 45 publications

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“…Therefore, MVs function as acellular nanoparticle vaccines that protect against the pathogens from which they are derived. In clinical settings, MVs of group B meningococci have been used not only as a vaccine against invasive meningococcal disease since the 1980s 5 , but, very recently, also as a promising adjuvant against SARS-CoV-2 6 .…”

Section: Introductionmentioning

confidence: 99%

A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles

et al. 2022

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Vaccines against infectious diseases should elicit potent and long-lasting immunity, ideally even in those with age-related decline in immune response. Here we report a rational polysaccharide vaccine platform using probiotic Escherichia coli-derived membrane vesicles (MVs). First, we constructed a probiotic E. coli clone harboring the genetic locus responsible for biogenesis of serotype 14 pneumococcal capsular polysaccharides (CPS14) as a model antigen. CPS14 was found to be polymerized and mainly localized on the outer membrane of the E. coli cells. The glycine-induced MVs displayed the exogenous CPS14 at high density on the outermost surface, on which the CPS14 moiety was covalently tethered to a lipid A-core oligosaccharide anchor. In in vivo immunization experiments, CPS14+MVs, but not a mixture of free CPS14 and empty MVs, strongly elicited IgG class-switch recombination with a Th1/Th2-balanced IgG subclass distribution without any adjuvant. In addition, CPS14+MVs were structurally stable with heat treatment and immunization with the heat-treated MVs-elicited CPS14-specific antibody responses in mouse serum to levels comparable to those of non-treated CPS14+MVs. Notably, the immunogenicity of CPS14+MVs was significantly stronger than those of two currently licensed vaccines against pneumococci. The CPS14+MV-elicited humoral immune responses persisted for 1 year in both blood and lung. Furthermore, the CPS14+MV vaccine was widely efficacious in mice of different ages. Even in aged mice, vaccination resulted in robust production of CPS14-specific IgG that bound to the pneumococcal cell surface. Taken together, the present probiotic E. coli MVs-based vaccine platform offers a promising, generalizable solution against encapsulated pathogens.

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Section: Introductionmentioning

confidence: 99%

A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles

et al. 2022

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“…This is a dimeric RBD vaccine where two RBD subunits are linked via an engineered single-chain construct and administered with Alum adjuvant as a three-dose schedule 8 . A similar dimeric RBD vaccine, combined with Alum plus Neisseria meningitidis outer membrane vesicles, is also in phase I clinical trials 50 . Another RBD-human IgG1-Fc dimer, fused to IFN-α and an MHC class-II binding element, combined with Alum adjuvant, has also recently been through phase I and II clinical trials 40, 51 and beta and delta VOC versions of this are in preclinical testing 52 .…”

Section: Discussionmentioning

confidence: 99%

“…RBD protein vaccines are in various stages of development and testing(https://covid19.trackvaccines.org/vaccines) 8,37,40,41,[49][50][51][52][53][54][55][56][57][58] , and one, ZF2001 8,50 , is now approved for emergency use in several countries, including China, Uzbekistan, Indonesia and Columbia (https://covid19.trackvaccines.org/vaccines/27/). This is a dimeric RBD vaccine where two RBD subunits are linked via an engineered single-chain construct and administered with Alum adjuvant as a three-dose schedule 8 .…”

Section: Severalmentioning

confidence: 99%

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine

Deliyannis

Gherardin

Wong

et al. 2022

Preprint

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The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Here, we report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid alpha-Galactosylceramide, or MF59 squalene oil-in-water adjuvant. Each formulation drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. We have also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the highly immunoevasive beta variant (N501Y, E484K, K417N). This beta variant RBD vaccine, combined with MF59 adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a third dose booster vaccine following priming with whole spike vaccine, anti-sera from beta-RBD-Fc immunised mice increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1 and BA.2. These results demonstrated that an RBD-Fc protein subunit/MF59 adjuvanted vaccine can induce high levels of broad nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain Spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial.

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“…The Finlay Institute responded to the pandemic developing Soberana 01, which uses RBD as antigen and vesicles from N. meningitidis from serogroup B and alum as adjuvants. In mice, they observed that this formulation was more immunogenic than RBD only adsorbed in Alum: it induced robust B-cell memory and neutralizing antibodies; thus, the antibodies recognized mutant RBD from SARS-CoV-2 variants [39]. Considering clinical use, the group described that the vaccine was safe and immunogenic, and the OMVs contributed to inducing functional, neutralizing antibodies [45].…”

Section: Covid-19 Vaccines -Current State and Perspectivesmentioning

confidence: 99%

Outer Membrane Vesicles: A Challenging Yet Promising Platform for COVID-19 Vaccines

Portilho¹,

Gaspari²

2023

COVID-19 Vaccines - Current State and Perspectives

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The outer membrane vesicles (OMVs) are vesicles released from Gram-negative bacteria, which present a range of biological applications, such as vaccine adjuvants. OMVs present several pathogen-associated molecular patterns, being immunogenic and capable of triggering different arms of the immune response. Thus, they are suitable for mucosal and parenteral delivery, feasible to obtain and have been used in licensed-vaccines previously. However, the extraction protocols and manipulations can modify OMVs cargo and, consequentially, the immunization results. Therefore, this chapter will review OMVs use as adjuvant and discuss results from COVID-19 vaccines which employed this technique.

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A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and Neisseria meningitidis outer membrane vesicles

Abstract: SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host’s cellular receptor. Vaccines seek to block this interaction by eliciting...

Cited by 16 publications

References 45 publications

A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles

A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine

Outer Membrane Vesicles: A Challenging Yet Promising Platform for COVID-19 Vaccines

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