Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Suthar, Mehul S.; Zimmerman, Matthew G.; Kauffman, Robert C.; Mantus, Grace; Linderman, Susanne L.; Hudson, William Henry; Vanderheiden, Abigail; Nyhoff, Lindsay E.; Davis, Carl W.; Adekunle, Oluwaseyi; Affer, Maurizio; Sherman, Melanie A.; Reynolds, Stacian; Verkerke, Hans; Alter, David; Guarner, Jeannette; Bryksin, Janetta; Horwath, Michael; Arthur, Connie M.; Saakadze, Natia; Smith, Geoffrey H.; Edupuganti, Srilatha; Scherer, Erin M.; Hellmeister, Kieffer; Cheng, Andrew; Morales, Juliet; Neish, Andrew S.; Stowell, Sean R.; Frank, Filipp; Ortlund, Eric A.; Anderson, Evan J.; Menachery, Vineet D.; Rouphael, Nadine; Mehta, Aneesh K.; Stephens, David S.; Ahmed, Rafi; Roback, John D.; Wrammert, Jens

doi:10.1016/j.xcrm.2020.100040

Cited by 484 publications

(522 citation statements)

References 21 publications

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“…While it fortunately appears that SARS-CoV-2 and many of the vaccine candidates in clinical trials can readily stimulate immune responses, (see e.g. (Corbett et al, 2020; Feng et al, 2020; Mulligan et al, 2020; Suthar et al, 2020; Wu, S. et al, 2020)), stringent assessment of antigens and careful selection of delivery vehicles are still necessary before it comes to mass vaccination. Careful selection of antigens is critical for avoiding unfavorable immune reactions and disease enhancement, as in the past experienced with RSV, measles and dengue vaccines (for reviews see (Lee et al, 2020; Ruckwardt et al, 2019)).…”

Section: Discussionmentioning

confidence: 99%

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Hennrich

Banda

Oberhuber

et al. 2020

Preprint

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The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which may cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients. Boost immunization with the identical replicon further enhanced neutralizing activity. These results demonstrate that rhabdovirus minispike replicons represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen.

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Section: Discussionmentioning

confidence: 99%

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Hennrich

Banda

Oberhuber

et al. 2020

Preprint

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“…The ∆NA(RBD)-Flu virus stably maintains the gene encoding the RBD over multiple passages, and cells infected with this virus express high levels of RBD on their surface. An intranasal inoculation of mice with a single dose of ∆NA(RBD)-Flu elicits neutralizing antibodies against SARS-CoV-2 in mice, with titers comparable to those observed in humans following natural infection [33,43,44] or an administration of two doses of a mRNA-based vaccine in clinical trials [20]. Notably, the ∆NA(RBD)-Flu elicited these neutralizing antibody titers after just a single intranasal inoculation at a viral dose that is lower than that typically used for live-attenuated influenza vaccines [4,13,45].…”

Section: Discussionmentioning

confidence: 95%

Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice

Loes

Gentles

Greaney

et al. 2020

Viruses

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An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.

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“…In this context, vaccines represent a much expected resource. A hopeful premise is represented by the successful containment of coronavirus epidemics in farm animals by vaccines, based on either killed or attenuated virus (160), and concerning SARS-CoV-2 by the finding that specific antibodies are detectable in 100% of patients with COVID-19, 17-19 days after symptom onset (161), and that the magnitude of antibody titers positively correlated with viral neutralization potency (162).…”

Section: Vaccinesmentioning

confidence: 99%

Viral Emerging Diseases: Challenges in Developing Vaccination Strategies

et al. 2020

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In the last decades, a number of infectious viruses have emerged from wildlife or reemerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.

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Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Cited by 484 publications

References 21 publications

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice

Viral Emerging Diseases: Challenges in Developing Vaccination Strategies

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