An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines

Hauser, Michael I.; Muscatello, DJ; Soh, Annabel C.Y.; Dwyer, Dominic E.; Turner, Robin

doi:10.1016/j.vaccine.2019.06.039

Cited by 19 publications

(21 citation statements)

References 42 publications

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“…The MF59 emulsion has been used in human in uenza vaccines for 2 decades, and extensive data show that it has a stronger protective effect than adjuvant-free in uenza vaccines and it increases the breadth and duration of the immune response in people of different ages [15,16] . However, serum protection against drifting viruses was as low as 20% in older subjects, which fails to meet the serum protection criteria set by the Committee for Medicinal Products for Human Use (CHMP) [17] .…”

Section: Discussionmentioning

confidence: 99%

The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens 

Shan

Wang

et al. 2021

Preprint

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Background New recombinant protein vaccines with high purity, clear ingredients and good safety are gradually replacing attenuated and inactivated vaccines in clinical practice. However, one of the main issues with use of these new vaccines is the need for adjuvants to enhance their immune effect. Aluminium salts (hydroxide and phosphate) were the first approved adjuvants used in human vaccines, but these salts have some limitations, such as their induction of primarily humoural immunity with weaker induction of cell-mediated immunity and the failure to clear intracellular viral infections. Therefore, there is a growing need for novel adjuvants. Combined adjuvants or adjuvant systems are increasingly being used to meet the need for adjuvant development for vaccines. Different pathogen antigens also need specific adjuvants to enhance the immune response and protection. Methods The present study evaluated the synergistic immunological effect of a combined nano emulsion (NE) with Ginsenoside Rg1, i.e. NE+Rg1, for the hepatitis B surface antigen (HBsAg) or H1N1 haemagglutinin (HA) of an inactivated influenza vaccine (split virion) in mice and the vaccine stability and safety. Non-parametric tests (Mann-Whitney test) and one-way analysis of variance (ANOVA) were used for statistical analyses. Tests were considered significant when P < 0.05.ResultsThe combined adjuvant NE+Rg1 showed high stability, a mean diameter of 168.1 nm, and a zeta potential of -22.8 mV. When combined with HBsAg, it produced a similar or higher anti-HB and IgG1/IgG2a titre and elevated IL-2 and IFN-γ expression in spot forming cells (SFCs) compared with NE alone and higher IFN-γ and IL-2 expression in CD8+ T cells than aluminium hydroxide. However, when combined with HA, HA+NE+Rg1 resulted in a comparable haemagglutination inhibition (HAI) titre as HA+NE compared to that in mice immunized with HA alone or HA+Rg1 and an even lower protection rate than HA+NE after PR/8/34 virus strain challenge in mice. Conclusions This research demonstrated that the same combined adjuvant NE+Rg1 had different immune effects on different antigens and suggests that the research and development of adjuvants must consider specific pathogens and should be studied on a case-by-case basis.

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Section: Discussionmentioning

confidence: 99%

The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens 

Shan

Wang

et al. 2021

Preprint

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“…Aluminium containing vaccines were associated with an increased risk of local events compared to unadjuvanted vaccines (26) (Supplementary Table 3). In adults, the risk of local adverse events after vaccination with oil-in water adjuvant containing vaccines (AS03 or MF59) was higher compared to vaccination with unadjuvanted vaccines (25,26). The increased risk was significantly higher for AS03 adjuvanted vaccines compared to MF59 adjuvanted vaccines, RR = 2.90 (95% CI 2.37-3.54) for AS03 and RR = 1.70 (95% CI 1.25-2.31) for MF59, subgroup difference p< 0.004 (25).…”

Section: Short-term Adverse Eventsmentioning

confidence: 99%

Safety of Influenza A H1N1pdm09 Vaccines: An Overview of Systematic Reviews

et al. 2021

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BackgroundIn 2009, a new influenza A H1N1 virus emerged causing a global pandemic. A range of monovalent influenza A H1N1pdm09 vaccines with or without adjuvants were developed. After the mass vaccination campaigns safety concerns related to H1N1pdm09 vaccines were reported. More than a decade later, reported AEFIs are still under scrutiny. We performed a systematic review aiming to synthesize the evidence on the safety of the H1N1pdm09 vaccines on reported outcomes from existing systematic reviews.MethodsFour electronic databases, PubMed, EMBASE, Epistimonikos and the Cochrane Database of Systematic Reviews were searched for articles on H1N1pdm09 vaccination published from 2009 to January 2021. Systematic reviews assessing short- or long-term adverse events after H1N1pdm09 vaccination were considered for inclusion. Data was extracted from all selected reviews. Outcomes were grouped and results from each included review were presented narratively and in tables.Results16 systematic reviews met the inclusion criteria. Reported outcomes were short-term events (3 reviews), fetal/pregnancy outcomes (8 reviews), Guillain-Barré syndrome (GBS) (4 reviews), narcolepsy (2 reviews) demyelinating diseases (1 review based on one study only) and inflammatory bowel disease (IBD) (1 review). Short-term serious adverse events were rare, 3 cases amongst 16725 subjects in 18 randomized controlled trials (0.018%). No deaths were reported. The risks of local events were generally higher for adjuvanted vaccines as compared to unadjuvanted vaccines. Maternal H1N1pdm09 vaccination in any trimester was not associated with an increase in preterm birth, small for gestational age, congenital malformations or fetal death. For GBS, results were conflicting. The main systematic review on narcolepsy found a 5-14-fold increased risk in children, and a 2-7- fold increased risk in adults after vaccination with Pandemrix. The attributable risk of narcolepsy one year after vaccination was 1 case per 18 400 vaccine doses in children/adolescents, and 1 case per 181 000 vaccine doses in adults.ConclusionAdjuvanted vaccines had more local but not serious adverse events compared to unadjuvanted vaccines. Vaccination with Pandemrix was strongly associated with narcolepsy, particularly in children. No increased risks of pregnancy outcomes were seen after pandemic vaccination. The findings on GBS were inconclusive.

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“…Three systematic reviews on short-term adverse events were included (25,26,33). These reviews included only RCTs.…”

Section: Short-term Adverse Eventsmentioning

confidence: 99%

“…Hauser reported a possible increase in local adverse events with MF59 adjuvanted vaccines in children but had no information on AS03 adjuvanted pandemic vaccine. The Hauser review (25) was assessed to high quality, the Manzoli review (26) to moderate and the Stassijns review (33) to low quality (Table 2).…”

Section: Short-term Adverse Eventsmentioning

confidence: 99%

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An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines

Cited by 19 publications

References 42 publications

The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens

The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens

Safety of Influenza A H1N1pdm09 Vaccines: An Overview of Systematic Reviews

Table_5.docx

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An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines

Cited by 19 publications

References 42 publications

The Same Combined Adjuvant NE+Rg1&nbsp;Shows Different Immune Effects on Different Pathogen Antigens&nbsp;

The Same Combined Adjuvant NE+Rg1&nbsp;Shows Different Immune Effects on Different Pathogen Antigens&nbsp;

Safety of Influenza A H1N1pdm09 Vaccines: An Overview of Systematic Reviews

Table_5.docx

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The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens

The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens