Poor Vaccine Effectiveness against Influenza B-Related Severe Acute Respiratory Infection in a Temperate North Indian State (2019–2020): A Call for Further Data for Possible Vaccines with Closer Match

Background: Influenza vaccine uptake in India is poor, and scant data exist regarding the effectiveness of influenza vaccine against hospitalization. Methods: From October 2019 to March 2020, vaccination status of 1219 patients (males n = 571, aged 5–107 years; median, 50 years) hospitalized with severe acute respiratory illness (SARI) was assessed. The patients were tested for influenza viruses and their subtypes by RT PCR. Sequencing of the HA gene was performed. Vaccine effectiveness (VE) against influenza subtypes was estimated by the test negative design. Results: A total of 336 (27.5%) patients were influenza-positive, with influenza B/Victoria accounting for 49.7% (n = 167), followed by influenza A/H1N1 (47.6%; n = 155) and influenza A/H3N2 (4.4%; n = 15). About 6.8% and 8.6% of the influenza-positive and influenza-negative patients, respectively, had been vaccinated. Adjusted VE for any influenza strain was 13% (95% CI −42 to 47), which for influenza B was 0%. HA sequencing revealed that influenza B samples mainly belonged to subclade V1A.3/133R with deletion of residues 163–165, as against the 2-aa deletion in influenza B/Colorado/06/2017 strain, contained in the vaccine. VE for influenza A/H1N1 was 55%. Conclusions: Poor VE due to a genetic mismatch between the circulating strain and the vaccine strain calls for efforts to reduce the mismatch.