Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans

Abstract

Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone ® , mammalian cell-derived Flucelvax ® or recombinant HA (Flublok ® ). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.

Highly pathogenic avian influenza A/Guangdong/17SF003/2016 is immunogenic and induces cross-protection against antigenically divergent H7N9 viruses

“…Previous studies reported that recombinant HA (rHA) expressed by the baculovirus/insect system shows good immunogenicity 14 – 16 . We next assessed the immunogenicity and protection of baculovirus-expressed H7 rHAs (Supplemental Fig.…”

“…Mice immunized with adjuvanted SH/2 or HK/125 rHA had virus-specific antibodies in similar level and quality to those administered with adjuvanted GD/16 rHA at 500 ng/mouse and were protected from the lethal HPAI wt GD/16 challenge. In humans, Flublok® based on baculovirus-expressed rHA was reported to elicit superior antibody responses than inactivated egg- or cell-based influenza vaccines 16 . Human antibodies elicited by AH/1 rHA vaccination were reported to broadly cross-react with emerging H7 HAs 15 .…”

Balanced Cellular and Humoral Immune Responses Targeting Multiple Antigens in Adults Receiving a Quadrivalent Inactivated Influenza Vaccine

“…Although subunit vaccines are generally considered to have limited capacity to boost cellular responses [ 23 ], recent studies have reported the induction of significant HA–specific CD4 T cell responses by Flucelvax [ 7 , 10 ]. While little is still known about the CD8 responses and their protein targets contained in this vaccine, here, we evaluated both CD4 and CD8 responses.…”

“…For the 2018–2019 influenza season, Flucelvax was designed to contain two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B virus strains (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) [ 5 ]. Compared to conventional egg-based influenza vaccines, its production can be expanded to large-scale within a short timeframe without egg-specific adaptions and mutations [ 7 ]. Since licensure in 2016, studies have shown that Flucelvax is potentially superior to egg-based vaccines in preventing influenza infection both in terms of real-life effectiveness, as well as in the protective efficacy demonstrated during clinical trials [ 8 ].…”

Next-Generation Influenza HA Immunogens and Adjuvants in Pursuit of a Broadly Protective Vaccine

“…Likewise, removal of these glycans, either through enzymatic means or through the use of alternative cell culture systems, to generate less-glycosylated HAs could afford enhanced breadth of protection. Studies investigating this hypothesis have demonstrated success in achieving wider protection and cross-reactivity by utilizing monoglycosylated and alternatively deglycosylated HA immunogens [ 34 , 35 , 36 , 37 ]. Specifically, treatment of embryonated chicken eggs with kifunensine, an inhibitor of α-mannosidase I-mediated glycosylation, in embryonated egg-based vaccine production, and virions with endoglycosidase H to trim their glycans to a monoglycosylated form, produced vaccines with superior HAI and neutralizing titers in mice [ 37 ].…”