Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity?

Moreno‐Fierros, Leticia; García-Silva, Ileana; Rosales‐Mendoza, Sergio

doi:10.1080/14712598.2020.1767062

Cited by 67 publications

(62 citation statements)

References 36 publications

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“…First, the vaccine induces neutralizing antibodies with a just single dose. Second, live influenza viruses induce mucosal immune responses [10,13,15,51] that may be important for protective immunity to SAR-CoV-2 [17,52]. Third, it might be possible to leverage additional influenza-virusengineering approaches such as those described in [11] to generate virions that express NA as well as RBD, and could serve as dual influenza-and SARS-CoV-2 vaccines.…”

Section: Discussionmentioning

confidence: 99%

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Loes

Gentles

Greaney

et al. 2020

Preprint

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An effective vaccine is essential to controlling the spread of 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 (~1:250). 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 production of influenza vaccines.

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Section: Discussionmentioning

confidence: 99%

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Loes

Gentles

Greaney

et al. 2020

Preprint

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“…Many vaccines are given via the intramuscular route, including the majority of the current COVID-19 vaccines in development ( Table 1 ). However, since SARS-CoV-2 causes infection via the respiratory tract, a vaccine targeting the mucosal immune system might be preferable ( 77 ). Mucosal vaccines have the advantage of being needle-free and thus practical for mass-administration, but immune tolerance induction can be an issue.…”

Section: Different Vaccine Approaches Used In Covid-19 Vaccine Develomentioning

confidence: 99%

“…An oral probiotic pill-based SARS-CoV-2 DNA vaccine (bacTRL) is also planned for clinical trials ( Table 1 ). The sublingual route is also considered an attractive route for inducing mucosal immunity ( 77 ). An alternative approach is to combine parenteral vaccines with adjuvants such as retinoic acid and CAF01 which are known to induce protective IgA mucosal responses ( 79 , 80 ).…”

Section: Different Vaccine Approaches Used In Covid-19 Vaccine Develomentioning

confidence: 99%

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

et al. 2020

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There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery.

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“…Efforts are being made to identify candidate neutralizing antibodies (Nabs) that could block the interaction of SARS-CoV2-S with its receptor and that could be used for treating infected patients (20)(21)(22). Several vaccine strategies for COVID-19 are also intensively pursued, with S protein being the major target (23)(24)(25). These vaccines are produced from different platforms: RNA, DNA, recombinant proteins, viral vector-based or virus-like particles (VLPs), and live attenuated and inactivated viruses (23)(24)(25).…”

mentioning

confidence: 99%

“…Several vaccine strategies for COVID-19 are also intensively pursued, with S protein being the major target (23)(24)(25). These vaccines are produced from different platforms: RNA, DNA, recombinant proteins, viral vector-based or virus-like particles (VLPs), and live attenuated and inactivated viruses (23)(24)(25).…”

mentioning

confidence: 99%

Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein

S¹,

Ghani

et al. 2020

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that started in China at the end of 2019 has rapidly spread to become pandemic. Several investigational vaccines that have already been tested in animals and humans were able to induce neutralizing antibodies against the SARS-CoV-2 spike (S) protein, however protection and long-term efficacy in humans remain to be demonstrated.We have investigated if a virus-like particle (VLP) derived from Moloney murine leukemia virus (MLV) could be engineered to become a candidate SARS-CoV-2 vaccine amenable to mass production. First, we showed that a codon optimized version of the S protein could migrate efficiently to the cell membrane. However, efficient production of infectious viral particles was only achieved with stable expression of a shorter version of S in its C-terminal domain (ΔS) in 293 cells that express MLV Gag-Pol (293GP). The incorporation of ΔS was 15-times more efficient into VLPs as compared to the full-length version, and that was not due to steric interference between the S cytoplasmic tail and the MLV capsid. Indeed, a similar result was also observed with extracellular vesicles released from parental 293 and 293GP cells. The amount of ΔS incorporated into VLPs released from producer cells was robust, with an estimated 1.25 μg/ml S2 equivalent (S is comprised of S1 and S2). Thus, a scalable platform that has the potential for production of pan-coronavirus VLP vaccines has been established. The resulting nanoparticles could potentially be used alone or as a boost for other immunization strategies for COVID-19.IMPORTANCESeveral candidate COVID-19 vaccines have already been tested in humans, but their protective effect and long-term efficacy are uncertain. Therefore, it is necessary to continue developing new vaccine strategies that could be more potent and/or that would be easier to manufacture in large-scale. Virus-like particle (VLP) vaccines are considered highly immunogenic and have been successfully developed for human papilloma virus as well as hepatitis and influenza viruses. In this study, we report the generation of a robust Moloney murine leukemia virus platform that produces VLPs containing the spike of SARS-CoV-2. This vaccine platform that is compatible with lyophilization could simplify storage and distribution logistics immensely.

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Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity?

Cited by 67 publications

References 36 publications

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein

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