A Cell Culture–Derived MF59-Adjuvanted Pandemic A/H7N9 Vaccine Is Immunogenic in Adults

Abstract

A potentially deadly A/H7N9 avian-origin influenza virus is currently the cause of an ongoing outbreak in China. Preparedness plans have thus been initiated to preempt the spread of this virus, which appears to have substantial pandemic potential. To effectively prevent a pandemic from unfolding, rapid production of an immunogenic vaccine with an acceptable safety profile is critical. Given the significance to public health, we are reporting immunogenicity and safety results from a phase 1 study in healthy adults administered one of four inactivated A/H7N9 vaccine formulations. Three formulations contained increasing quantities of antigen and of an oil-in-water adjuvant, MF59, and one formulation contained only the maximum dose of antigen without adjuvant. All vaccine formulations were derived using a synthetic virus seed technology in combination with a cell culture approach; together, these techniques have been shown to expedite vaccine production compared to conventional methods. Higher responses were seen with the MF59-adjuvanted versus the nonadjuvanted A/H7N9 vaccine, with significant and potentially protective immune responses after two doses in most subjects with no preexisting immunity to the H7N9 virus. Further, despite increased injection site pain and other mild effects with MF59, all formulations were well tolerated. These encouraging immunogenicity and safety data on the A/H7N9 vaccine provide a strong rationale for further clinical development. By also using synthetic seed/cell culture technology, we are now one step closer to being able to rapidly and reliably respond to a potential H7N9 pandemic using a clinically tested A/H7N9 vaccine.

Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes

“…Accumulated evidence has demonstrated that A(H7N9) vaccines have poor immunogenicity without an adjuvant. Even at a higher dosage of 45 g of HA, only minimal antibody responses were induced (32), while the incorporation of an adjuvant, such as MF-59, and Iscomatrix in the A(H7N9) vaccine formation enhanced the immunogenicity significantly (30,31). Thus, the conventional vaccination regimen may not be adequate to elicit the optimal neutralization antibody response unless a higher antigen dose or adjuvant or immune potentiation measures are considered (33)(34)(35).…”

“…Currently, the development of A(H7N9) vaccines has encountered the problems of a low seroconversion rate and low titer of antibody response in animal models and several human clinical trials (28)(29)(30)(31). Accumulated evidence has demonstrated that A(H7N9) vaccines have poor immunogenicity without an adjuvant.…”

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

“…Clinical development of influenza vaccines is ongoing, however split virus or subunit vaccines for avian influenza are known to be poorly immunogenic (26,27) and often require multiple doses and/or formulation with potent adjuvants to achieve seroconversion (28). Although live attenuated vaccines (LAIVs) can induce of both humoral and cellular immunogenicity, in adults these vaccines have previously been associated with lower seroconversion rates and higher rates of laboratory-confirmed influenza when compared to trivalent influenza vaccine.…”

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

“…20 The results of alternative vaccine strategies have also been subpar with both inactivated H7N9 split vaccine and H7N9 HA virus-like particle vaccine eliciting HI seroconversion rates of only 6% and 15.6% in Phase I trials respectively. 21,22 This compares poorly with the ~ 89% rate reported for similar seasonal influenza subunit vaccines. 23–25 Even with the addition of adjuvant and a booster injection, the inactivated split H7N9 vaccine elicited HI seroconversion in only 59% of subjects in an early Phase II clinical trial.…”