Compositions and methods of live attenuated alphavirus formulations
A composition and alpha virus technology, applied in biochemical equipment and methods, antiviral agents, viruses, etc., can solve problems such as vaccine inactivation, temperature limit sensitivity, etc.
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Embodiment 1
[0101] Buffer screening
[0102] In certain exemplary methods, liquid and lyophilizable compositions suitable for use in preclinical and clinical trials and alphavirus vaccines are identified. One consideration with regard to liquid compositions according to these exemplary compositions is that some alphaviruses are pH sensitive (eg sensitive to low pH). Accordingly, the components of the compositions disclosed herein include a carefully considered pH factor. In certain exemplary compositions, the pH of the formulation is from about pH 6 to about 10, with many formulations having a pH of about pH 6.5-7.5 and up to about 9.5.
[0103] In some approaches, attenuated Chikungunya virus (hereinafter CHIK) is used as an example of an alphavirus composition in preclinical and clinical trials.
[0104] Compositions for use in these methods are provided. In an exemplary experiment, predetermined amounts of CHIK-IRES vaccine (pMVS), where the attenuated virus is controlled by IRES in...
Embodiment 2
[0108] In some other exemplary approaches, based on the observation that inclusion of one or more carbohydrates has a positive effect on CHIK vaccine stability, long-term stability experiments at 4°C were performed to analyze the effect of different carbohydrates (e.g., sugars) on alphaviruses. Effects on Stability of Vaccines (eg CHIK Virus Vaccine). Compositions containing HEPES and carbohydrates such as sucrose, lactose, trehalose, galactose, fructose, D-sorbitol, dextrose and D-mannitol) are produced. Aliquots of predetermined concentrations of CHIK-IRES vaccine (pMVS) were formulated in these compositions and incubated at 4°C for 12 weeks. exist figure 2 Samples were collected and titrated to Vero cells at the time points indicated. Such as figure 2 It was shown that the composition of about 15% trehalose, 15% sucrose or 10% D-mannitol combined with HEPES buffered saline (HB) showed about the same effect on virus stability as other compositions, better than other com...
Embodiment 3
[0112] Screening of formulations for protein-induced stability
[0113] In other exemplary methods, different protein agents are assayed for increasing the stability of alphavirus formulations compared to controls (no protein or with unfavorable other proteins). Compositions containing HB or HBS and the protein agent of interest were analyzed. In each experimental condition about 10 5 After incubation (~21 hours at 37°C) of the attenuated CHIK vaccine composition, an aliquot was taken and passed through TCID 50 Growth in Vero cells was titrated. Then, evaluate the percentage of remaining virus titer. Such as Figure 4 Addition of gelatin to formulations with or without carbohydrates increases the stability of alphavirus vaccines at 37°C as shown in (see Figure 4 ).
[0114] Figure 4 Shows exemplary total percentages of CHIK virus titers remaining after ~21 hours of incubation in a composition containing HEPES-buffered saline and proteins such as lactoferrin, tryptone,...
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