Single-vial filovirus glycoprotein vaccines: Biophysical characteristics and immunogenicity after co-lyophilization with adjuvant

Preston, Kendall B.; Wong, Teri Ann S.; To, Albert; Tashiro, Taylor Emi; Lieberman, Michael M.; Granados, Alex; Feliciano, Karen; Harrison, Joseph G.; Yalley-Ogunro, Jake; Elyard, Hanne Andersen; Donini, Oreola; Lehrer, Axel T.; Randolph, Theodore W.

doi:10.1016/j.vaccine.2021.08.003

Cited by 14 publications

(17 citation statements)

References 42 publications

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“…Antigen-specific IFN-γ production after splenocyte restimulation ex vivo was more variable, but also increased with the use of adjuvant, particularly after two doses, and was not strongly dependent on adjuvant concentration. These robust responses in outbred mice observed with relatively low antigen and adjuvant doses are particularly encouraging in light of our previous work which has demonstrated the successful thermostabilization of this adjuvant in combination with other glycoprotein antigens [66] . More recently, we have demonstrated that these recombinant subunits, in combination with CoVaccine HT™, can be formulated as a glassy solid using lyophilization.…”

Section: Discussionsupporting

confidence: 55%

Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

Lai

Wong

et al. 2021

Vaccine: X

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Section: Discussionsupporting

confidence: 55%

Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

Lai

Wong

et al. 2021

Vaccine: X

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“…An advantage of recombinant subunit protein vaccines compared to virally vectored vaccine platforms is that the lead antigen may be thermostabilized alone or together with an adjuvant to withstand a wider range of temperatures thus easing the logistics of distribution and deployment especially to resource-poor and isolated regions where maintaining a cold chain is difficult (56,57). The non-infectious nature of this platform also does not exclude the medically vulnerable (e.g., immunocompromised populations), thereby increasing recipient reach (19,(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

“…These adjuvants have acceptable safety profiles and have been well-tolerated in clinical trials, with mostly localized and mild systemic adverse effects reported (30,41,(97)(98)(99)(100)(101)(102). This is encouraging as both saponin extracts and CFASE have been lyophilized without compromising immunostimulatory function (57,103). This may enable the development of a thermostabilized vaccine which may be beneficial if a vaccine were to be deployed to areas where maintaining a cold chain is difficult as is the case for most LASV endemic areas.…”

Section: A B D Cmentioning

confidence: 97%

Adjuvants Differentially Modulate the Immunogenicity of Lassa Virus Glycoprotein Subunits in Mice

To¹,

Lai²,

Wong³

et al. 2022

Front. Trop. Dis

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Lassa Fever (LF) is an acute viral hemorrhagic fever caused by Lassa virus (LASV) that is primarily transmitted through contact with wild rodents in West Africa. Although several advanced vaccine candidates are progressing through clinical trials, some effective vaccines are virally vectored and thus require a stringent cold-chain, making distribution to rural and resource-poor areas difficult. Recombinant subunit vaccines are advantageous in this aspect as they can be thermostabilized and deployed with minimal storage and transportation requirements. However, antigen dose and adjuvant formulation must be carefully selected to ensure both the appropriate humoral and cell-mediated immune responses are elicited. In this study, we examine the immunogenicity of a two-step immunoaffinity-purified recombinant LASV glycoprotein (GP) with five clinical- and preclinical-grade adjuvants. Swiss Webster mice immunized intramuscularly with 2 or 3 doses of each vaccine formulation showed complete seroconversion and maximal GP-specific antibody response after two immunizations. Formulations with GPI-0100, LiteVax, Montanide™ ISA 51, and Montanide™ ISA 720 induced both IgG1 and IgG2 antibodies suggesting a balanced Th1/Th2 response, whereas formulation of LASV GP with Alhydrogel elicited a IgG1-dominant response. Splenocytes secreting both Th1 and Th2 cytokines i.e., IFN-γ, TNF-α, IL-2, IL-4 and IL-5, were observed from mice receiving both antigen doses formulated with ISA 720, LiteVax and GPI-0100. However, robust, multifunctional T-cells were only detected in mice receiving a higher dose of LASV GP formulated with GPI-0100. Our results emphasize the importance of careful adjuvant selection and lay the immunological basis for a recombinant subunit protein LF vaccine formulation.

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“…The RiVax antigen is compatible with other adjuvants such LT-II (34,35) and alpha-galactosyl ceramide (36), but, to our knowledge, RiVax adsorbed to aluminum hydroxide has not itself been combined with other adjuvants. Moreover, whether such adjuvants would be compatible with the RiVax lyophilization protocol would also need to be investigated (17), although success with a similar lyophilized formulation and a nano-emulsion adjuvant (CoVaccine HT™) has been demonstrated (37).…”

Section: Discussionmentioning

confidence: 99%

Durable Immunity to Ricin Toxin Elicited by a Thermostable, Lyophilized Subunit Vaccine

Novak

Doering

Ehrbar

et al. 2021

Preprint

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The development of vaccines against biothreat toxins like ricin (RT) is considered an integral component of the United States national security efforts. RiVaxÒ is a thermostable, lyophilized RT subunit vaccine adsorbed to aluminum salt adjuvant intended for use by military personnel and first responders. Phase 1 studies indicated that RiVax is safe and immunogenic, while a three dose, intramuscular vaccination regimen in non-human primates elicited protection against lethal dose RT challenge by aerosol. Here we investigated, in a mouse model, the durability of RiVax-induced antibody responses and corresponding immunity to lethal dose RT challenge. Groups of mice were subcutaneously administered 3 or 1 μg of RiVax on days 0 and 21 and challenged with 10 ´ LD50 RT by injection at six different intervals over the course of twelve months. Serum antibody titers and epitope-specific competition assays were determined prior to each challenge. We report that the two-dose, 3 μg regimen conferred near complete protection against RT challenge on day 35 and complete protection thereafter (challenge days 65, 95, 125, 245, and 365). The two-dose, 3 μg regimen was superior to the 1 μg regimen as revealed by slight differences in survival and morbidity scores (e.g., hypoglycemia, weight loss) on challenge days 35 and 365. In separate experiments, a single 3 μg RiVax vaccination proved only marginally effective at eliciting protective immunity to RT, underscoring the necessity of a prime-boost regimen to achieve full and long-lasting protection against RT.

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Single-vial filovirus glycoprotein vaccines: Biophysical characteristics and immunogenicity after co-lyophilization with adjuvant

Cited by 14 publications

References 42 publications

Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

Adjuvants Differentially Modulate the Immunogenicity of Lassa Virus Glycoprotein Subunits in Mice

Durable Immunity to Ricin Toxin Elicited by a Thermostable, Lyophilized Subunit Vaccine

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