key: cord-0285327-ypkpqlnd
authors: Díez, José María; Casals, Daniel; Romero, Carolina; Gajardo, Rodrigo
title: Seasonal IVIG contains high infectivity neutralizing and hemagglutination inhibition activity against seasonal flu virus strains selected for vaccines (2020-22)
date: 2022-02-02
journal: bioRxiv
DOI: 10.1101/2022.01.31.478469
sha: df831f7cb62cfc34423faab670b41178b1880907
doc_id: 285327
cord_uid: ypkpqlnd

IVIG solutions (10%) were tested for infectivity neutralization and hemagglutination inhibition against the influenza strains (two A and two B) recommended by the WHO for inclusion in vaccines for Northern and Southern hemispheres 2020-2022. The IVIG batches used were manufactured (June 2020) from plasma pools collected in the US. Potent neutralization and inhibition of hemagglutination were seen with these IVIG batches. This raises the possibility that IVIG could be added to existing therapies, especially in immunocompromised patients, to fight serious influenza infections. Further study of the potential of IVIG in influenza is warranted.

Seasonal influenza viruses are a major global public health problem year after year with the possible exception of this past year due to anti-COVID-19 pandemic safety measures. Recent global estimates of the mortality burden of influenza are in range of 290,000-650,000 deaths annually. 1, 2 The flu season in most of the world was very mild in 2020-2021. 3 As previously mentioned, this was likely due in part to the public health measures implemented to control the COVID-19 pandemic (e.g., masking, physical distancing, restrictions on large indoor and outdoor gatherings). 4, 5 With the foreseeable decline in COVID-19 cases in many parts of the world, the public health measures in place for the last two years would be lifted. This could lead to a rebound in influenza cases for the 2021-2022 season and thereafter with case levels well above those expected for a normal flu season. 3 Vaccination is currently one of the best available countermeasures In this study, IVIG solutions manufactured in June 2020 (from plasma collected in the prior 6-months) were tested for activity against the four influenza strains recommended in February 2020 for the Northern Hemisphere 2020-2021 influenza season, 6 the strains subsequently recommended in September 2020 for the Southern Hemisphere 2021 influenza season 7 and in February 2021 for the Northern Hemisphere 2021-2022 season. 8 Activity was measured using neutralization and hemagglutination inhibition assays.

The influenza viruses used in these studies were obtained from National Institute for Biological Standards and Controls NIBSC (Ridge, Herts, UK). Viral strains selected by the WHO for the quadrivalent influenza vaccine usually contain two A strains (H1N1 and H3N2) and two B strains (Victoria lineage and After one hour of incubation at 37°C, the 0.75% solution of chicken erythrocytes (25 µL) was added to all wells. The plates were incubated for one hour at room temperature and then read. Results were reported as the highest dilution of IVIG that inhibited hemagglutination. Table 1 

In the circumstances of viral resistance and/or a lack of effectiveness of the usual treatments, additional prophylactic or treatment options are needed.

The data presented here show that this seasonal IVIG (June 2020) had high hemagglutination inhibition and neutralization titers against the influenza strains selected for inclusion in seasonal flu vaccines. These results raise the potential that IVIG could be used together with the aforementioned treatment strategies to help control seasonal influenza epidemics. Immunocompromised patients, those with comorbidities and the general population could potentially benefit from IVIG treatment. In any case, this possibility deserves and needs more investigation. 

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