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Heterologous viral protein interactions within licensed seasonal influenza virus vaccines.

ABSTRACT: Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In the studies reported here, we have examined the viral protein composition of a panel of licensed vaccines from different manufacturers and licensed in different years. Using western blotting, we found that, beyond HA proteins, there are detectable quantities of neuraminidase (NA), nucleoprotein (NP), and matrix proteins (M1) from both influenza A and influenza B viruses in the vaccines but that the composition differed by source and method of vaccine preparation. We also found that disparities in viral protein composition were associated with distinct patterns of elicited antibody specificities. Strikingly, our studies also revealed that many viral proteins contained in the vaccine form heterologous complexes. When H1 proteins were isolated by immunoprecipitation, NA (N1), M1 (M1-A), H3, and HA-B proteins were co-isolated with the H1. Further biochemical studies suggest that these interactions persist for at least 4 h at 37 °C and that the membrane/intracytoplasmic domains in the intact HA proteins are important for the intermolecular interactions detected. These studies indicate that, if such interactions persist after vaccines reach the draining lymph node, both dendritic cells and HA-specific B cells may take up multiple viral proteins simultaneously. Whether these interactions are beneficial or harmful to the developing immune response will depend on the functional potential of the elicited virus-specific CD4 T cells.

SUBMITTER: Koroleva M

PROVIDER: S-EPMC6954117 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Several candidates of universal influenza vaccine (UIV) have entered phase III clinical trials, which are expected to improve the willingness and coverage of the population substantially. The impact of UIV on the seasonal influenza epidemic in low influenza vaccination coverage regions like China remains unclear. We proposed a new compartmental model involving the transmission of different influenza subtypes to evaluate the effects of UIV. We calibrated the model by weekly surveillance data of influenza in Xi'an City, Shaanxi Province, China, during 2010/11-2018/19 influenza seasons. We calculated the percentage of averted infections under 2-month (September to October) and 6-month (September to the next February) vaccination patterns with varied UIV effectiveness and coverage in each influenza season, compared with no UIV scenario. A total of 195 766 influenza-like illness (ILI) cases were reported during the nine influenza seasons (2010/11-2018/19), of which the highest ILI cases were among age group 0-4 (59.60%) years old, followed by 5-14 (25.22%), 25-59 (8.19%), 15-24 (3.75%) and ⩾60 (3.37%) years old. The influenza-positive rate for all age groups among ILI cases was 17.51%, which is highest among 5-14 (23.75%) age group and followed by 25-59 (16.44%), 15-24 (16.42%), 0-4 (14.66%) and ⩾60 (13.98%) age groups, respectively. Our model showed that UIV might greatly avert influenza infections irrespective of subtypes in each influenza season. For example, in the 2018/19 influenza season, 2-month vaccination pattern with low UIV effectiveness (50%) and coverage (10%), and high UIV effectiveness (75%) and coverage (30%) could avert 41.6% (95% CI 27.8-55.4%) and 83.4% (80.9-85.9%) of influenza infections, respectively; 6-month vaccination pattern with low and high UIV effectiveness and coverage could avert 32.0% (15.9-48.2%) and 74.2% (69.7-78.7%) of influenza infections, respectively. It would need 11.4% (7.9-15.0%) of coverage to reduce half of the influenza infections for 2-month vaccination pattern with low UIV effectiveness and 8.5% (5.0-11.2%) of coverage with high UIV effectiveness, while it would need 15.5% (8.9-20.7%) of coverage for 6-month vaccination pattern with low UIV effectiveness and 11.2% (6.5-15.0%) of coverage with high UIV effectiveness. We conclude that UIV could significantly reduce the influenza infections even for low UIV effectiveness and coverage. The 2-month vaccination pattern could avert more influenza infections than the 6-month vaccination pattern irrespective of influenza subtype and UIV effectiveness and coverage.

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Heterologous viral protein interactions within licensed seasonal influenza virus vaccines.

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