Preparedness against pandemic influenza: Production of an oil-in-water emulsion adjuvant in Brazil

Abstract

Increasing pandemic influenza vaccine manufacturing capacity is considered strategic by WHO. Adjuvant use is key in this strategy in order to spare the vaccine doses and by increasing immune protection. We describe here the production and stability studies of a squalene based oil-in-water emulsion, adjuvant IB160, and the immune response of the H7N9 vaccine combined with IB160. To qualify the production of IB160 we produced 10 consistency lots of IB160 and the average results were: pH 6.4±0.05; squalene 48.8±.0.03 mg/ ml; osmolality 47.6±6.9 mmol/kg; Z-average 157±2 nm, with polydispersity index (PDI) of 0.085±0.024 and endotoxin levels <0.5 EU/mL. The emulsion particle size was stable for at least six months at 25˚C and 24 months at 4-8˚C. Two doses of H7N9 vaccine formulated at 7.5 μg/dose or 15 μg/dose with adjuvant IB160 showed a significant increase of hemagglutination inhibition (HAI) titers in sera of immunized BALB/c mice when compared to control sera from animals immunized with the H7N9 antigens without adjuvant. Thus the antigensparing capacity of IB160 can potentially increase the production of the H7N9 pandemic vaccine and represents an important achievement for preparedness against pandemic influenza and a successful North (IDRI) to South (Butantan Institute) technology transfer for the production of the adjuvant emulsion IB160.

Dose-sparing effect of two adjuvant formulations with a pandemic influenza A/H7N9 vaccine: A randomized, double-blind, placebo-controlled, phase 1 clinical trial

“…In this regard, the squalene-based oil-in-water emulsion vaccine adjuvant MF59 and AS03 have been administered to more than 200 million people in more than 30 countries, in both seasonal and pandemic influenza vaccines with a safe and efficacious profile since 1997 [ 34 ]. IB160 is also a squalene emulsion-based adjuvant with minor differences to MF59 [ 11 ]. IB160 was developed at Butantan Institute through a Technology Transfer agreement with Infectious Diseases Research Institute (Seattle, USA) with the support of BARDA and WHO for preparedness of a pandemic influenza response.…”

“…Two squalene oil-in-water emulsion adjuvant formulations were evaluated concerning their H7N9 influenza antigen dose-sparing effects. IB160 was manufactured by IB and SE was manufactured by the Infectious Disease Research Institute (IDRI) and donated to IB for this trial [ 11 , 12 ]. Both formulations were stored in a 10 mL vial containing 1.5 mL.…”

“…Similar to MF59, IB160 adjuvant is composed of Squalene, Span 85, Tween 80 in citrate buffer. However, they differ in concentration of the components and Ph ranges [ 11 ]. SE is a stable oil-in water emulsion, where the oil concentration is 2% (v/v), composed of the excipients squalene (oil), glycerol, egg phosphatidylcholine, surfactant (poloxamer) and ammonium phosphate buffer [ 12 ].…”

“…SE is a stable oil-in water emulsion, where the oil concentration is 2% (v/v), composed of the excipients squalene (oil), glycerol, egg phosphatidylcholine, surfactant (poloxamer) and ammonium phosphate buffer [ 12 ]. The H7N9 antigen combined with squalene-based oil-in-water emulsion formulations demonstrated to be immunogenic and to have acceptable safety profiles in mice and ferrets [ 9 – 11 ].…”

Better Pandemic Influenza Preparedness through Adjuvant Technology Transfer: Challenges and Lessons Learned

“…There are multiple reports detailing successful influenza manufacturing technology transfers that have improved production capacities in LMICs [ 26 , 27 , 28 , 29 ]. However, there are only a few publications that have reported on adjuvant technology transfer, namely the transfer of oil-in-water emulsion adjuvant manufacturing technologies [ 30 , 31 , 32 , 33 ]. The transfer of adjuvant technologies and training of local staff, combined with the setting up of adequate facilities, would facilitate vaccine research and development in LMICs and support members of the vaccine community, such as public sector institutions, small biotechnology companies, and vaccine developers [ 34 , 35 ].…”