Comparison of A(H3N2) Neutralizing Antibody Responses Elicited by 2018-2019 Season Quadrivalent Influenza Vaccines Derived from Eggs, Cells, and Recombinant Hemagglutinin.

BACKGROUND: Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. METHODS: Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018-2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. RESULTS: All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019-2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. CONCLUSION: Egg- and cell-derived 2018-2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.

Health Maintenance Deficits in a Fully Insured Population of Adolescents With Chronic Medical Conditions.

The current national monitoring of routine wellness care and vaccine uptake does not provide data on health maintenance among pediatric populations with chronic medical conditions. In this case-control study that analyzes wellness visits and vaccine uptake among adolescents, ages 16 to 18 years, we identified 938 without (controls) and 74 with (cases) 1 of 12 specific chronic medical conditions. The PPSV23 (23-valent pneumococcal polysaccharide vaccine) is recommended by the Advisory Committee on Immunization Practices for these 12 conditions and served as a measure of uptake for medically indicated vaccines. Our controls were twice as likely as cases to have a documented well visit in the past year, and there was a significantly higher proportion of controls than cases vaccinated with Tdap (tetanus toxoid, reduced diphtheria toxoid, acellular pertussis), MCV-4 (quadrivalent meningococcal conjugate), and HPV (human papillomavirus), all P < .05. More than 60% of cases failed to receive PPSV23. Adolescents with chronic medical conditions are at high risk of neglecting routine health maintenance.