Buffer free, acid stable low dose volume rotavirus vaccine
Inventors
Vadrevu, Krishna Mohan • Prasad, Sai Devarajulu • Ella, Krishna Murthy
Assignees
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Publication Number
US-11351245-B2
Publication Date
2022-06-07
Expiration Date
Abstract
A buffer free, acid stable, low dose volume rotavirus vaccine is disclosed. The vaccine is available in dose volume of less than 1 ml per dose for oral administration and it is without any buffer. The vaccine also does not require pre or post administration of any antacid at the time of oral administration of the vaccine to the subject to neutralize the stomach acid. The vaccine exemplifies nominal drop in vaccine titer at pH 2-4 for a time span of 30 minutes. The vaccine is stable at −20° C. for at least 60 months.
Core Innovation
The invention relates to a liquid rotavirus vaccine composition comprising a live attenuated rotavirus of strain 116E and a formulation that contains no buffer or antacid. The composition is provided with a dose volume of 0.5 ml and includes sucrose at a concentration of 50% together with specified concentrations of lactose or trehalose and lactalbumin hydrolysate, plus recombinant human serum albumin.
The disclosure addresses the need for acid protection for oral rotavirus vaccination while maintaining infectivity and immune response under acidic conditions without relying on buffer and antacid administration. It frames the approach as avoiding pre/during/post antacid administration while preserving required infectivity and immune response.
The buffer-free and acid-stable approach maintains virus performance, including measured titer losses after exposure to pH 2–4, with stability testing showing virus withstands acid without buffer. The document further describes assessment of formulation acid neutralization capacity and multicenter clinical trial results with comparable anti-rotavirus IgA GMTs, seroconversion, and safety whether ROTAVAC® is given with citrate-bicarbonate buffer or without buffer.
Claims Coverage
The document includes three independent claims covering distinct liquid rotavirus vaccine compositions based on live attenuated rotavirus strain 116E formulated with sucrose and specified combinations of carbohydrates and excipients. Each independent claim further requires that the composition contains no buffer or antacid and that the dose volume is 0.5 ml, with dependent claims adding rotavirus titre and/or storage/maintainable temperature-duration constraints.
Buffer-free liquid rotavirus vaccine with sucrose, lactose, lactalbumin hydrolysate, and rHSA at 0.5 ml dose volume
A liquid rotavirus vaccine composition comprising a live attenuated rotavirus of strain 116E; sucrose at a concentration of 50%; lactose at a concentration of 0.5%; lactalbumin hydrolysate at a concentration of 0.05%; and recombinant human serum albumin at a concentration of 0.5%, wherein the composition contains no buffer or antacid, and wherein the composition has a dose volume of 0.5 ml.
Buffer-free liquid rotavirus vaccine with sucrose, trehalose, lactalbumin hydrolysate, and rHSA at 0.5 ml dose volume
A liquid rotavirus vaccine composition comprising a live attenuated rotavirus of strain 116E; sucrose at a concentration of 50%; trehalose at a concentration of 0.5%; lactalbumin hydrolysate at a concentration of 0.5%; and recombinant human serum albumin at a concentration of 0.5%, wherein the composition contains no buffer or antacid, and wherein the composition has a dose volume of 0.5 ml.
Buffer-free liquid rotavirus vaccine with sucrose, higher trehalose, lactalbumin hydrolysate, and rHSA at 0.5 ml dose volume
A liquid rotavirus vaccine composition comprising a live attenuated rotavirus of strain 116E; sucrose at a concentration of 50%; trehalose at a concentration of 1.0%; lactalbumin hydrolysate at a concentration of 0.5%; and recombinant human serum albumin at a concentration of 0.5%, wherein the composition contains no buffer or antacid, and wherein the composition has a dose volume of 0.5 ml.
Across the independent claims, the main claim coverage is directed to a 0.5 ml liquid rotavirus vaccine containing live attenuated rotavirus strain 116E with specified sucrose plus carbohydrate and excipient combinations, while explicitly requiring that no buffer or antacid is present.
Stated Advantages
Provides a buffer-free and acid-stable liquid rotavirus vaccine composition that does not require pre/during/post antacid administration.
Maintains infectivity and immune response despite absence of buffer or antacid.
Shows comparable anti-rotavirus IgA GMTs and seroconversion and includes reactogenicity and safety whether ROTAVAC® is given with citrate-bicarbonate buffer or without buffer.
Provides stability of the formulations under multiple storage conditions, including storage stability at ≤-20°C, 2–8°C, 25°C, and 37°C.
Documented Applications
Multicenter clinical trial use in which ROTAVAC® is administered with citrate-bicarbonate buffer or without buffer, assessing anti-rotavirus IgA GMTs, seroconversion, and reactogenicity/safety.
Oral administration of a live attenuated rotavirus 116E vaccine in a buffer-free formulation with no buffer or antacid.
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