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MF59 adjuvanted flu vaccine more protective than nonadjuvanted vaccine
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Recent data show the adjuvant MF59 increases the immunogenicity of inactivated influenza vaccines among unvaccinated children.
Luisanna Zedda, PhD, of Novartis Vaccines, and colleagues randomized 84 unvaccinated children, aged 6 to 36 months, to receive two intramuscular doses of a non-adjuvanted trivalent influenza vaccine (TIV) or adjuvanted MF59 TIV 4 weeks apart. The phase 2 study was conducted at two sites in Belgium.
Most of the reported local and systemic adverse events were mild to moderate intensity and were resolved within a few days after vaccination. Children who received adjuvanted TIV were more likely to report adverse events, although the events were mild to moderate; tenderness at the injection site most common event reported after the first dose, according to the study findings.
Both vaccines induced a significant increase of hemagglutination inhibition (HI) antibodies against vaccine strains A/H1N1California, A/H3N2Victoria, and B/Brisbane. Adjuvanted TIV induced a significant increase in HI antibodies against strains A/Uruguay and B/Malaysia, which are heterologous to strains within the vaccine. Adjuvanted TIV induced significantly higher HI antibody titers for A/H3N2Victoria, B/Brisbane, and B/Malaysia than TIV.
HI titers for A/H1N1California were higher after adjuvanted TIV compared with TIV, but the difference was not statistically significant.
It is important to note HI titers were higher for A/H1N1California compared with AH3N2Victoria and B/Brisbane prior to vaccination, according to researchers.
Both vaccines met all of the Committee for Medicinal Products for Human Use criteria for influenza A strains. The adjuvanted vaccine met all criteria for influenza B strain. However, TIV did not meet seroprotection standards for influenza B strain, as only 57% of children had HI titers of at least 1:40.
Adjuvanted TIV induced expansion of CD4 cells for homologous A/H1N1California, A/H3N2Victoria, B/Brisbane and heterologous B/Florida influenza antigens. TIV induced expansion of CD4 cells for A/H1N1California and A/H3N2Victoria. The increase of CD4 cells for A/H1N1California was not statistically different after TIV vs. adjuvanted TIV. However, the increase of CD4 cells for A/H3N2Victoria and B/Brisbane was significantly higher after adjuvanted TIV compared with TIV.
“The data presented here strongly support the advantage of using the MF59-adjuvanted TIV over the non-adjuvanted TIV in priming an immune response in immunologically naive subjects, like young children, and to widen the breadth of the response to heterologous virus strains. We conclude that MF59-adjuvanted influenza vaccines are safe and immunogenic in children and support its use in this age group to confer higher and broader protection in unprimed children,” the researchers concluded.
Disclosure: The study was funded by Novartis Vaccines.
Perspective
Back to TopKathryn M. Edwards, MD
In this manuscript, the authors compare and contrast the humoral and cell-mediated immune responses in children who have received trivalent seasonal influenza vaccine (TIV) with and without MF59 adjuvant. Although a larger study previously published in the New England Journal of Medicine showed that the adjuvanted TIV vaccine was highly effective in preventing laboratory-confirmed influenza, much better than the unadjuvanted TIV vaccine, this study adds an immunologic perspective.
Children receiving the adjuvanted TIV had higher antibody responses to both the vaccinating strain and the heterovariant strains and also had a larger expansion of the CD4 T cells. As clearly shown in this paper, adjuvants are potent enhancers of immune responses. However the recent association of narcolepsy with another adjuvant administered with H1N1 pandemic influenza vaccine, AS03, has added a note of caution to the use of all similar adjuvants in children.
What can we do to assure adjuvant safety? First, we can use sophisticated immunologic studies, such as systems biology to dissect the differences in the biologic effects of the different adjuvants. Second, we can continue to pursue answers to what actually happened biologically in the children who developed narcolepsy. Was the response specific to this influenza strain or directed to the adjuvant? Third, we can carefully weigh the risks and the benefits of adjuvants. During a pandemic of avian H7 influenza with a high mortality, the use of an adjuvant to markedly improve the immune response would certainly be a risk worth taking. This study is an important one to help us dissect the impact of potent adjuvants on immune responses.
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