HCV E1E2/MF59C / Novartis - LARVOL DELTA

IgA binds to the AD-2 epitope of glycoprotein B and neutralizes Human Cytomegalovirus. (PubMed, Immunology) - "This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine...V-region matched AD-2 specific recombinant IgG and IgA bound both to gB and AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk which may function to protect neonates from HCMV."

Journal • Cytomegalovirus Infection

An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines. (PubMed, Vaccine) - "Despite limited studies, in adults, AS03-adjuvanted vaccines allow antigen sparing versus MF59-adjuvanted and unadjuvanted vaccines, with similar immunogenicity, but higher risk of pain and fatigue (secondary outcomes) than unadjuvanted vaccines. In children, adjuvanted vaccines are also superior, but the better adjuvant is uncertain."

Journal • Retrospective data • Review • Fatigue • Infectious Disease • Pain • Pediatrics

Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults. (PubMed, J Infect Dis) - "Some acute local reactions were more frequent following vaccination with MF59-adjuvanted and high-dose influenza vaccines compared to standard-dose inactivated influenza vaccine, while systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population."

Clinical • Journal • Infectious Disease

Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults (clinicaltrials.gov) - P1/2; N=334; Not yet recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1/2 trial • Biosimilar • Gene Therapies • Immunology

Incidence of narcolepsy before and after MF59-adjuvanted influenza A(H1N1)pdm09 vaccination in South Korean soldiers. (PubMed) - "The incidence of narcolepsy in South Korean soldiers was not increased after the pandemic vaccination campaign using the MF59-adjuvanted vaccine. Our results suggest that the MF59-adjuvanted H1N1 vaccine did not contribute to the occurrence of narcolepsy in this young adult group."

Journal • Biosimilar

Narcolepsy and Pandemic Influenza Vaccination: What We Need to Know to be Ready for the Next Pandemic. (PubMed, Pediatr Infect Dis J) - "No studies have identified an increased risk of narcolepsy following the MF59-adjuvanted Focetria vaccine...Thus, it is critical that we understand the nature of the association between adjuvanted vaccine receipt and narcolepsy. Here, we present a potential hypothesis for narcolepsy seen during the 2009 H1N1 pandemic in AS03-adjuvanted influenza vaccine recipients."

Journal

Effectiveness of influenza vaccine in reducing influenza-associated hospitalizations and deaths among the elderly population; Lazio region, Italy, season 2016-2017. (PubMed, Expert Rev Vaccines) - "We found no significant differences in effectiveness by vaccine type, although the MF59-adjuvanted vaccine appeared more effective than other vaccines in individuals aged ≥75 years, particularly in those aged ≥90 years (VE=18%, 95%CI: 9 to 26). Although VE was low, vaccination still provided benefits in preventing influenza-related hospitalizations and deaths in the elderly, particularly among those vaccinated in prior seasons. Efforts should therefore be made to improve vaccine uptake and the utilization of vaccines with greater effectiveness in the oldest elderly (e.g., high-dose and adjuvanted cell-based vaccines)."

Clinical • Journal

Effectiveness, immunogenicity, and safety of influenza vaccines with MF59 adjuvant in healthy people of different age groups: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "The quality of evidence is moderate to high for seroconversion and seroprotection rates of influenza vaccine. MF59-adjuvanted influenza vaccines are superior to non-adjuvanted influenza vaccines to enhance immune responses of vaccination in healthy adults and older adults, and could be considered for routine use especially the monovalent prepandemic influenza vaccines."

Journal • Retrospective data • Review

Comparative immunogenicity of enhanced seasonal influenza vaccines in older adults: a systematic review and meta-analysis. (PubMed, J Infect Dis) - "High-dose vaccine elicited 82% higher postvaccination titer to A(H3N2) compared with SD vaccine; this was significantly higher than the 52% estimated for MF59-adjuvanted versus SD vaccines (P = .04), which was higher than the 32% estimated for intradermal versus SD vaccines (P < .01). Overall, by summarizing current evidence, we found enhanced vaccines had greater antibody responses than standard-dose vaccine. Indications of differences among enhanced vaccines highlight that further research is needed in order to compare new vaccine options; this is especially needed during seasons with mismatched circulating strains and for immune outcomes other than HAI titers as well as vaccine efficacy."

Journal • Retrospective data • Review

Meeting report narcolepsy and pandemic influenza vaccination: What we know and what we need to know before the next pandemic? A report from the 2nd IABS meeting. (PubMed, Biologicals) - "There was consensus that an increased risk of narcolepsy was consistently observed after Pandemrix (AS03-adjuvanted) vaccine, but similar associations following Arepanrix (AS03-adjuvanted) or Focetria (MF59-adjuvanted) vaccines were not observed...The limitations of retrospective observational methodologies could also be contributing to some of the differences across studies. More basic and epidemiologic research is needed to further elucidate the association between adjuvanted influenza vaccine and narcolepsy and its mechanism and to inform planning and preparation for vaccination programs in advance of the next influenza pandemic."

Journal

Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. (PubMed, Clin Infect Dis) - P4; "In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients."

Clinical • Journal

Safety and immunogenicity of influenza A(H5N1) vaccine stored up to twelve years in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS). (PubMed, Vaccine) - P2; "The frequency, type, and severity of AEs observed during this study are similar to historical clinical study data with A(H5N1) vaccines and MF59 adjuvant indicating that a stockpiled A(H5N1) vaccine appears to remain safe and tolerable. The vaccines were immunogenic when administered as a two-dose vaccine regimen in healthy adults, despite extended storage of HA antigen or MF59 adjuvant within the NPIVS."

Clinical • Journal

Intrahost dynamics of human cytomegalovirus variants acquired by seronegative glycoprotein B vaccinees. (PubMed, J Virol) - "The glycoprotein B (gB) plus MF59 adjuvant subunit vaccine is the most efficacious tested clinically to date, demonstrating 50% protection against primary HCMV infection in a phase 2 clinical trial...Here, we used viral DNA isolated from patients enrolled in a gB vaccine trial who acquired HCMV, and identified several impacts that this vaccine had on the size, distribution, and composition of the in vivo viral population. These results have increased our understanding of why the gB/MF59 vaccine was partially efficacious, and such investigations will inform future rational design of a vaccine to prevent congenital HCMV."

Journal

Immunology and efficacy of MF59-adjuvanted vaccines. (PubMed, Hum Vaccin Immunother) - "CD4-independent adjuvant effects of MF59 might contribute to improving the vaccine efficacy in children, the elderly, and immunocompromised patients as well as in healthy adults. Further studies will be needed to broaden the use of MF59 in various vaccine antigens and populations as well as lead to better understanding of the action mechanisms of MF59 adjuvant."

Clinical • Journal

Cumulative Clinical Experience with MF59-Adjuvanted Trivalent Seasonal Influenza Vaccine in Young Children. (PubMed, Int J Infect Dis) - "aIIV3 was well tolerated, with immunogenicity and efficacy exceeding that of conventional IIV3 in children 6 months through 5years of age. The MF59-adjuvanted vaccine has the potential to fulfill an unmet clinical need in the prevention of seasonal influenza in this age group."

Clinical • Journal

Immunogenicity of Influenza Vaccines: Evidence for Differential Effect of Secondary Vaccination on Humoral and Cellular Immunity. (PubMed, Front Immunol) - "We evaluated both antibody and T cell responses in a cohort of public health care workers (18-52 years) during two consecutive influenza seasons from 2009 to 2011 and compared the MF59-adjuvanted pandemic vaccine with the unadjuvanted seasonal subunit vaccine that included the pandemic strain [The study was registered in the Netherlands Trial Register (NTR2070)]...In addition, residual antibody levels remained detectable for over 15 months, while T cell levels in the blood had contracted to baseline levels by that time. Hereby, we show that pandemic as well as seasonal vaccines induce both humoral and cellular responses, however, with a different profile of induction and waning, which has its implications for future vaccine design."

Journal

The adjuvant effects of MF59 on antigen-specific regulatory and effector T cells (AAI 2019) - "...We thus investigated the effects of MF59-adjuvanted peptide vaccines on antigen-specific T cell immunity against influenza virus infection...Finally, MF59-peptide vaccines stimulated the production of IFN-γ and TNF-α of CD4 and CD8 T cells. In conclusion, MF59-peptide vaccine exhibits a unique feature in stimulation of antigen-specific T cell immunity"

Clinical