Egg- and cell-derived influenza vaccines administered during the 2018-2019 influenza seasons elicited similar neutralization titers and response rates, according to a study recently published in Clinical Infectious Diseases.

To prevent influenza virus infection, the most effective public health measure is vaccination. Effectiveness of inactivated influenza vaccines (IIV) has been variable in recent years, especially for A(H3N2) viruses. Most influenza vaccines used worldwide are manufactured in eggs, where egg-adaptive mutations can change hemagglutinin (HA) antigenicity resulting in a reduction in vaccine effectiveness. During the 2018-2019 influenza seasons, the influenza vaccine did not provide measurable protection against A(H3N2) due to the emergence of an antigenically drifted A(H3N2) variant. Newer influenza vaccines can avoid this by using manufacturing technologies with cell-derived vaccine viruses and recombinant HA (rHA) antigens.

Annual influenza vaccines are tested for appropriate antigenicity and adequate potency. HAs in each vaccine may vary in amino acid residues. A standard dose of rHA vaccine contains at least 45 µg of each HA antigen, while standard doses of IIVs contain at least 15 µg of each HA antigen. There is limited data directly comparing the neutralizing antibody responses of cell-derived IIV (cIIV) and rHA vaccine to that of the egg-derived IIV (eIIV) using each of the vaccine-matched HA antigens. This study compared neutralizing antibody responses in pre- and post-immunization sera from adults who received either eIIV, cIIV, or rHA vaccine during the 2018-2019 influenza season.

Included in this study were 133 adult military health beneficiaries who were vaccinated with eIIV (Fluarix), cIIV (Flucelvax) or rHA vaccine (Flublok) in the 2018-2019 influenza season. Each type of vaccine was administered to roughly one-third of the included subjects. Neutralization titers in pre- and post-immunization sera from the included subjects were measured against egg- and cell-derived A(H3N2) influenza viruses using HA-pseudoviruses. The codon-optimized H3 HAs were used to construct HA-pseudoviruses and test for sera neutralization. Serum samples were obtained pre-immunization (Day 0) and post-immunization (Days 21 through 35). Neutralizing antibody titers from Day 21 samples were presumed to be due to vaccination.

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Results suggest the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. There were similar pre-immunization neutralization titers against each of the H3 vaccine antigens in individuals who received the eIIV, cIIV, or rHA vaccine. Additionally, all vaccines induced neutralizing antibody responses. The highest titers and seroconversion rates against all tested strains were elicited from the rHA vaccine, which may be due to higher HA content. The egg- and cell-derived IIVs elicited similar responses. These results suggest that the higher HA content is the main reason for increased immunogenicity, rather than the absence of egg-adaptive substitutions.

Limitations of this study include unknown vaccination histories of included participants and a small sample size.

Overall, the study authors conclude that “[a]dditional studies comparing vaccine effectiveness to antibody responses elicited by vaccines with and without HA egg-adaptive substitutions are needed across many influenza seasons to inform vaccination policy.”


Wang W, Alvarado-Facundo E, Vassell R, et al. Comparison of A(H3N2) neutralizing antibody responses elicited by 2018-2019 season quadrivalent influenza vaccines derived from eggs, cells, and recombinant hemagglutinin. Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa1352/5902974.