Mechanism and application progress of MF59 adjuvant in influenza vaccine / 中国生物制品学杂志

@#Influenza vaccination is the most effective route to prevent influenza virus transmission,and adding adjuvant to influenza vaccines not only enhances the body immune response but also saves the antigen dose.In addition to the classic aluminum adjuvant,MF59 adjuvant is the second one on the market and has been widely used as adjuvant in human vaccine,which not only has an ability to induce antibody equivalent to that of aluminum adjuvant,but can induce cellular immune response,recruit immune cells,and improve the effectiveness of vaccine.In this review,the mechanism of action and current application progress of MF59 adjuvant in influenza vaccine was described,and the further development of MF59adjuvant research was put forward.

Adjuvant activity of alum adjuvant and MF59 for HIV-1 multi-epitope protein MEP1 / 中华微生物学和免疫学杂志

Objective To compare the adjuvant activity of oil-in-water emulsion MF59 and aluminum hydroxide on immune responses to HIV-1 multi-epitope protein MEP1 in BALB/c mice. Methods HIV-1 multi-epitope protein MEP1 with MF59 or aluminum was prepared to intramuscularly vaccinate female BALB/c mice for three times. Serum and splenocytes were isolated from the mice 10 d after the first and last vaccination. Specific anti-MEP1 antibodies and the subclasses in serum were detected by ELISA. The num-bers of splenic lymphocytes secreting IFN-γ and IL-4 were measured by ELISPOT. Differences in humoral and cellular immune responses induced by the two different adjuvants were compared. Results After a sin-gle-dose immunization, aluminum adjuvant promoted early humoral and cellular immune responses to MEP1 compared with MF59. After the three-dose immunization, both aluminum adjuvant and MF59 promoted MEP1 to induce Th2-biased humoral immune response, while MF59 also enhanced a balanced Th1/Th2 cel-lular immune response. Conclusions Aluminum adjuvant was a more suitable adjuvant than MF59 for HIV-1 multi-epitope protein MEP1.

Phase 4, Post-Marketing Safety Surveillance of the MF59-Adjuvanted Influenza Vaccines FLUAD® and VANTAFLU® in South Korean Subjects Aged ≥65 Years / 감염과화학요법

BACKGROUD: Influenza vaccination is recommended for adults aged ≥65 years as they are at high risk of significant morbidity and mortality. This open-label, multicenter, post-marketing surveillance study assessed the safety of the MF59-adjuvanted trivalent inactivated subunit influenza vaccine, which is marketed as FLUAD® and VANTAFLU®, in South Korean subjects aged ≥65 years. MATERIALS AND METHODS: Solicited local and systemic adverse events (AEs) were collected from day 1 to 4 of the study. All unsolicited AEs and serious AEs (SAEs) were recorded from day 1 until study termination (day 29). RESULTS: Of the 770 subjects enrolled (FLUAD®, n = 389; VANTAFLU®, n = 381), 39% overall experienced any solicited AE. Local AEs were reported by 33% of subjects overall; with the most common events being injection-site pain (30%) and tenderness (27%). Systemic AEs were reported by 19% of subjects overall with the most common events being myalgia (11%) and fatigue (8%). CONCLUSION: These results show that the MF59-adjuvanted influenza vaccine known as FLUAD® or VANTAFLU® had acceptable safety profiles in older adults (aged ≥65 years) in South Korea.

Phase 4, Post-Marketing Safety Surveillance of the MF59-Adjuvanted Influenza Vaccines FLUAD® and VANTAFLU® in South Korean Subjects Aged ≥65 Years / 감염과화학요법

BACKGROUD: Influenza vaccination is recommended for adults aged ≥65 years as they are at high risk of significant morbidity and mortality. This open-label, multicenter, post-marketing surveillance study assessed the safety of the MF59-adjuvanted trivalent inactivated subunit influenza vaccine, which is marketed as FLUAD® and VANTAFLU®, in South Korean subjects aged ≥65 years. MATERIALS AND METHODS: Solicited local and systemic adverse events (AEs) were collected from day 1 to 4 of the study. All unsolicited AEs and serious AEs (SAEs) were recorded from day 1 until study termination (day 29). RESULTS: Of the 770 subjects enrolled (FLUAD®, n = 389; VANTAFLU®, n = 381), 39% overall experienced any solicited AE. Local AEs were reported by 33% of subjects overall; with the most common events being injection-site pain (30%) and tenderness (27%). Systemic AEs were reported by 19% of subjects overall with the most common events being myalgia (11%) and fatigue (8%). CONCLUSION: These results show that the MF59-adjuvanted influenza vaccine known as FLUAD® or VANTAFLU® had acceptable safety profiles in older adults (aged ≥65 years) in South Korea.

Safety and Mechanism of Action of Licensed Vaccine Adjuvants.

Vaccines are some of the most effective tools for the prevention of infectious diseases. Adjuvants are included in vaccines for a variety of reasons: to increase the breadth of response, to lower antigen dose, to overcome limited immune response in some populations, or to enable complex combination vaccines. This study aims to review the safety of licensed vaccine adjuvants and describe their mechanism of action. Potential publications for inclusion were identified through a direct search of PubMed/Medline database. Results of online literature searches were supplemented by relevant papers cited in published studies along with the authors’ knowledge of published studies. To date, there are 5 licensed vaccine adjuvants in US and Europe: Aluminum salts (EU, US), MF59 (EU), AS03 (EU), AS04 (EU, US), and virosomes (EU). AS03 is not available as an adjuvant in other vaccines but included within the US government’s National Stockpile. All vaccines that contain these adjuvants have been proven safe in clinical trials and post-marketing studies, with the exception of the AS03, for which the rare events of narcolepsy have been reported in some countries. Every adjuvant has a complex and often multifactorial immunological mechanism, usually poorly understood in vivo. The safety profile of an adjuvant, including the actual and hypothetical risks, is a critical component that can speed up or impede adjuvant development. The increasing understanding in adjuvant sciences is fundamental to the further development of new adjuvants.

Evaluation of the efficacy of MF59 and Al (OH) 3 adjuvants in modifying HIV-1 gp140 trimer in-duced specific humoral immune response / 中华微生物学和免疫学杂志

Objective To evaluate the effectiveness of MF59 and Al( OH) 3 adjuvants in potentia-ting HIV-1 specific humoral immune response when used in combination with HIV-1 gp140 trimer.Methods Guinea pigs were randomly divided into three groups including the MF59 full dose treatment group ( antigen to adjuvant volume ratio:1 ∶1 ) , the MF59 half dose treatment group ( antigen to adjuvant volume ratio:1 ∶0.5) and the Al(OH)3 treatment group (antigen to adjuvant volume ratio:1 ∶1).The guinea pigs in each group were immunized with gp140 trimer and corresponding adjuvants for three times with three weeks interval between each injection.Serum samples were collected at week 9 for the detection of HIV-1 gp120 binding antibodies, HIV-1 gp70V1V2 binding antibodies and HIV-1 neutralizing antibodies against eight dif-ferent pseudoviruses of four different clades.Results Compared with the Al(OH)3 treatment group, the guinea pigs treated with full dose and half dose of MF59 showed significantly increased titers of HIV-1 gp120 binding antibodies (P=0.027 and P=0.041).The levels of HIV-1 gp70V1V2 binding antibodies in full dose of MF59 treated guinea pigs were significantly higher than those of Al( OH) 3 treated guinea pigs ( P=0.029).No significant difference with the HIV-1 gp70V1V2 binding antibodies was observed between the MF59 half dose treatment group and the Al( OH) 3 treatment group.The serum samples collected from each group could neutralize the eight different pseudoviruses at different degrees, except that two pseudoviruses of clade B ( REJO4541 and TRJO4551) could not be neutralized by serum samples from MF59 half dose treated guinea pigs.The MF59 full dose treatment group showed the highest geometric mean of 50%inhibitory dose (ID50) to the eight pseudoviruses, followed by Al(OH)3 treatment group and MF59 half dose treatment group.Conclusion Compared with the traditional Al(OH)3 adjuvant, full dose of MF59 adjuvant in com-bination with HIV-1 gp140 trimer could induce higher levels of binding antibodies against HIV-1 gp120 and HIV-1 gp70V1V2, as well as high levels of neutralizing antibodies.

Safety and Mechanism of Action of Licensed Vaccine Adjuvants.

Vaccines are some of the most effective tools for the prevention of infectious diseases. Adjuvants are included in vaccines for a variety of reasons: to increase the breadth of response, to lower antigen dose, to overcome limited immune response in some populations, or to enable complex combination vaccines. This study aims to review the safety of licensed vaccine adjuvants and describe their mechanism of action. Potential publications for inclusion were identified through a direct search of PubMed/Medline database. Results of online literature searches were supplemented by relevant papers cited in published studies along with the authors’ knowledge of published studies. To date, there are 5 licensed vaccine adjuvants in US and Europe: Aluminum salts (EU, US), MF59 (EU), AS03 (EU), AS04 (EU, US), and virosomes (EU). AS03 is not available as an adjuvant in other vaccines but included within the US government’s National Stockpile. All vaccines that contain these adjuvants have been proven safe in clinical trials and post-marketing studies, with the exception of the AS03, for which the rare events of narcolepsy have been reported in some countries. Every adjuvant has a complex and often multifactorial immunological mechanism, usually poorly understood in vivo. The safety profile of an adjuvant, including the actual and hypothetical risks, is a critical component that can speed up or impede adjuvant development. The increasing understanding in adjuvant sciences is fundamental to the further development of new adjuvants.

Fluad(R)-MF59(R)-Adjuvanted Influenza Vaccine in Older Adults / 감염과화학요법

Influenza directly or indirectly contributes to the four leading causes of global mortality, at rates that are highest in older adults. As the proportion of older adults in the Korean population is greater than in most other countries, influenza prevention is a greater public health priority in Korea than elsewhere. Conventional inactivated influenza vaccine (IIV) is less immunogenic and efficacious (-50%) in older than in young adults, but adjuvanting the vaccine with oil-in-water emulsion MF59(R) increases immunogenicity, resulting in comparatively higher levels of hemagglutination inhibition antibodies and greater protection against all influenza, as well as cases requiring hospitalization. A recent observational study demonstrated that the adjuvanted vaccine protected older adults against influenza in a year when nonadjuvanted IIV was ineffective. In another multiyear study, the adjuvanted vaccine was estimated to be 25% more effective in preventing pneumonia and influenza hospitalizations compared to nonadjuvanted vaccine. Although MF59-adjuvanted vaccine is transiently more reactogenic than nonadjuvanted vaccine, there is no evidence that it increases risks for serious adverse events, including those with an autoimmune etiology. Experience thus far indicates a favorable balance of benefit to risk for MF59. This may reflect the adjuvant's mechanism of action in which the squalene oil emulsion increases antibody responses to co-administered antigen without acting more generally as an immunopotentiator.