Comparison of purified psoralen-inactivated and formalin-inactivated dengue vaccines in mice and nonhuman primates

Sundaram, Appavu K.; Ewing, Daniel; Blevins, Maria; Liang, Zhaodong; Sink, Sandy; Lassan, Josef; Raviprakash, Kanakatte; Defang, Gabriel; Williams, M. C.; Porter, Kevin R.; Sanders, John W.

doi:10.1016/j.vaccine.2020.03.008

Cited by 20 publications

(21 citation statements)

References 25 publications

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“…A more common use of immunocompetent mice has been to evaluate the immunogenicity of DENV vaccine candidates [33][34][35]. Challenge of immunized mice can assess vaccine efficacy against morbidity and mortality when DENV is administered directly into the brain via intracranial injection route [36,37] or through intraperitoneal injection of DENVinfected hematopoietic tumor (e.g., K562) cells [38,39] (Table 1).…”

Section: Mouse Models Of Dengue Infection and Pathogenesismentioning

confidence: 99%

Dengue mouse models for evaluating pathogenesis and countermeasures

Chen

Diamond

2020

Current Opinion in Virology

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Dengue virus (DENV) causes the most prevalent arbovirus illness worldwide and is responsible for many debilitating epidemics. The four circulating DENV serotypes infect humans and can cause asymptomatic, mild, moderate, or severe Dengue. Because of the global morbidity and mortality due to Dengue, deployment of a safe and effective tetravalent vaccine has been a high priority, and to date, a partially realized goal. The study of pathogenesis and development of DENV therapeutics and vaccines has been limited by few animal models that recapitulate features of human disease. Over the past two decades, mouse models of DENV infection have evolved with increasing success. Here, we review the utilization and limitations of mice for studying DENV pathogenesis and evaluating countermeasures.

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Section: Mouse Models Of Dengue Infection and Pathogenesismentioning

confidence: 99%

Dengue mouse models for evaluating pathogenesis and countermeasures

Chen

Diamond

2020

Current Opinion in Virology

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“…Unlike β-propiolactone and formalin, psoralen inactivates viral pathogens at the nucleic acid level, thereby leaving surface viral proteins mostly undisturbed [11,12]. Using dengue virus, psoralen-inactivated vaccines generated superior neutralizing antibody responses compared to formalin-inactivated vaccines [12]. Employing a platform based on psoralen inactivation to develop a SARS-CoV-2 vaccine was therefore a logical approach.…”

Section: Discussionmentioning

confidence: 99%

“…We previously investigated the use of psoralen to inactivate all four serotypes of dengue virus and evaluated the immunogenicity of psoralen-inactivated dengue virus vaccines in mice and nonhuman primates [11,12]. Psoralen is a furanocoumarin that intercalates with nucleic acids and, upon exposure to long wave ultraviolet radiation, leads to interstrand cross-links by covalently binding to pyrimidine bases [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice

et al. 2021

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The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there are only three whole-virus vaccine candidates produced using β-propiolactone or formalin inactivation. Here, we prepared a whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) using a novel psoralen inactivation method and evaluated its immunogenicity in mice using two different adjuvants, alum and Advax-2. We compared the immunogenicity of SARS-CoV-2 PsIV against SARS-CoV-2 DNA vaccines expressing either full-length or truncated spike proteins. We also compared the psoralen-inactivated vaccine against a DNA prime, psoralen-inactivated vaccine boost regimen. After two doses, the psoralen-inactivated vaccine, when administered with alum or Advax-2 adjuvants, generated a dose-dependent neutralizing antibody responses in mice. Overall, the pattern of cytokine ELISPOT responses to antigen-stimulation observed in this study indicates that SARS-CoV-2 PsIV with the alum adjuvant promotes a Th2-type response, while SARS-CoV-2 PsIV with the Advax-2 adjuvant promotes a Th1-type response.

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“…As a possible alternative, inactivated dengue vaccine candidates have also been developed using inactivation methods that work at the nucleic acid level (photo-inactivation in the presence of a psoralen compound) rather than protein level, thereby leaving the antigenic structure of the virus in its native form [ 13 ]. These psoralen-inactivated dengue vaccine (PsIV) candidates elicited high levels of virus neutralizing antibodies in vaccinated mice and NHPs [ 13 , 14 ]. In addition, PsIV-induced T-cell responses have been shown to be equivalent to a live dengue virus vaccine candidate [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Immunogenicity of Inactivated Dengue Vaccines by Novel Polysaccharide-Based Adjuvants in Mice

Ewing

Sundaram

et al. 2022

Microorganisms

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Dengue fever, caused by any of four dengue viruses (DENV1-4), is a major global burden. Currently, there is no effective vaccine that prevents infection in dengue naïve populations. We tested the ability of two novel adjuvants (Advax-PEI and Advax-2), using aluminum hydroxide (alum) as control, to enhance the immunogenicity of formalin- or psoralen-inactivated (PIV or PsIV) DENV2 vaccines in mice. Mice were vaccinated on days 0 and 30, and serum samples were collected on days 30, 60, 90, and 101. Neutralizing antibodies were determined by microneutralization (MN) assays, and the geometric mean 50% MN (MN50) titers were calculated. For the PIV groups, after one dose MN50 titers were higher in the novel adjuvant groups compared to the alum control, while MN50 titers were comparable between the adjuvant groups after the second dose. For the PsIV groups, both novel adjuvants induced higher MN50 titers than the alum control after the second dose. Spleen cells were collected on days 45 and 101 for enzyme-linked immunospot (ELISPOT) for IFNγ and IL4. Both PIV and PsIV groups elicited different degrees of IFNγ and IL4 responses. Overall, Advax-2 gave the best responses just ahead of Advax-PEI. Given Advax-2’s extensive human experience in other vaccine applications, it will be pursued for further development.

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Comparison of purified psoralen-inactivated and formalin-inactivated dengue vaccines in mice and nonhuman primates

Cited by 20 publications

References 25 publications

Dengue mouse models for evaluating pathogenesis and countermeasures

Dengue mouse models for evaluating pathogenesis and countermeasures

Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice

Enhanced Immunogenicity of Inactivated Dengue Vaccines by Novel Polysaccharide-Based Adjuvants in Mice

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