Establishment of a Pseudovirus Platform for Neuraminidase Inhibiting Antibody Analysis.

Neuraminidase (NA)-based immunity to influenza can be useful for protecting against novel antigenic variants. To develop safe and effective tools to assess NA-based immunity, we generated a baculovirus-based pseudotyped virus, N1-Bac, that expresses the full-length NA of the influenza A/California/07/2009 (H1N1)pdm09 strain. We evaluated the level of NA-inhibiting (NI) antibodies in the paired blood sera of influenza patients by means of an enzyme-linked lectin assay (ELLA) using the influenza virus or N1-Bac. Additionally, we evaluated the level of NA antibodies by means of the enzyme-linked immunosorbent assay (ELISA) with an N1-expressing Sf21 culture. We detected a strong correlation between our results from using the influenza virus and NA-Bac pseudoviruses to detect NI antibodies and a medium-strong correlation between NI antibodies and NA antibodies determined by an N1-cell ELISA, indicating that baculovirus-based platforms can be successfully used to evaluate NI or NA antibodies. Furthermore, animal experiments showed that immunization with N1-Bac protected against infection with a drift variant of the A/H1N1pdm09 influenza virus. Our results demonstrate that recombinant baculovirus can be an effective influenza pseudotype to evaluate influenza serologic immunity and protect against influenza virus infection.

Age-Specific Etiology of Severe Acute Respiratory Infections and Influenza Vaccine Effectivity in Prevention of Hospitalization in Russia, 2018-2019 Season.

The expansion and standardization of clinical trials, as well as the use of sensitive and specific molecular diagnostics methods, provide new information on the age-specific roles of influenza and other respiratory viruses in development of severe acute respiratory infections (SARI). Here, we present the results of the multicenter hospital-based study aimed to detect age-specific impact of influenza and other respiratory viruses (ORV). The 2018-2019 influenza season in Russia was characterized by co-circulation of influenza A(H1N1)pdm09 and A(H3N2) virus subtypes which were detected among hospitalized patients with SARI in 19.3% and 16.4%, respectively. RSV dominated among ORV (15.1% of total cases and 26.8% in infants aged ≤ 2 years). The most significant SARI agents in intensive care units were RSV and influenza A(H1N1)pdm09 virus, (37.3% and 25.4%, respectively, of PCR-positive cases). Hyperthermia was the most frequently registered symptom for influenza cases. In contrast, hypoxia, decreased blood O2 concentration, and dyspnea were registered more often in RSV, rhinovirus, and metapneumovirus infection in young children. Influenza vaccine effectiveness (IVE) against hospitalization of patients with PCR-confirmed influenza was evaluated using test-negative case-control design. IVE for children and adults was estimated to be 57.0% and 62.0%, respectively. Subtype specific IVE was higher against influenza A(H1N1)pdm09, compared to influenza A(H3N2) (60.3% and 45.8%, respectively). This correlates with delayed antigenic drift of the influenza A(H1N1)pdm09 virus and genetic heterogeneity of the influenza A(H3N2) population. These studies demonstrate the need to improve seasonal influenza prevention and control in all countries as states by the WHO Global Influenza Strategy for 2019-2030 initiative.