Presence of defective viral genes in H1N1 live attenuated influenza vaccine strains is not associated with reduced human cell fitness or vaccine effectiveness

Ayaz, Sameer; Dibben, Oliver; Chapman, David

doi:10.1016/j.vaccine.2021.10.011

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…DVGs in segments 1-3 were detected in all 11 H1N1 LAIV strains tested; DVGs from PA made up the highest proportion (between 10.2% and 27.8% in different strains) of DVGs from any segment. This study also indicated that a higher proportion of PA DVGs does not impair the replication of the full-length viral genome in two strains [53].…”

Section: Potential Impact Of Dips On Immunogenicity Of Laivssupporting

confidence: 53%

“…In a low-proportion (76.58%) DIP group, the IFN-β expression level was 37-fold higher than that in a high-proportion (99.78%) DIP group in infected MDCK cells at 8 hpi [40]. Ayaz et al showed that the high-proportion (66.5%) PA DVG group induced a three-fold increase in IFN-β mRNA levels compared to the low-proportion (17.5%) PA DVG group, resulting in STV titer loss in primary human nasal epithelial cells [53]. When mice were challenged with IAV stocks containing a high proportion of DVGs or lacking DVGs, there was no significant difference in the total amount of replicated IAV genome in the first 3 days post-infection (dpi) between the two groups [54].…”

Section: Immune Activation and Underlying Mechanisms Of Influenza Vir...mentioning

confidence: 99%

“…The large amount of DVGs in LAIVs may be an important reason for the reduced effectiveness of FluMist ® , apart from prevalent strain prediction bias [19]. Another study by Ayaz et al examined DVGs in 11 historical H1N1 LAIV strains using digital RT-PCR [53]. DVGs in segments 1-3 were detected in all 11 H1N1 LAIV strains tested; DVGs from PA made up the highest proportion (between 10.2% and 27.8% in different strains) of DVGs from any segment.…”

Section: Potential Impact Of Dips On Immunogenicity Of Laivsmentioning

confidence: 99%

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Defective Interfering Particles of Influenza Virus and Their Characteristics, Impacts, and Use in Vaccines and Antiviral Strategies: A Systematic Review

Zhou

Sheng

et al. 2022

Viruses

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Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA viruses, especially in influenza viruses. Evidence indicates that DIPs interfere with the replication and encapsulation of wild-type viruses, namely standard viruses (STVs) that contain full-length viral genomes. DIPs may also activate the innate immune response by stimulating interferon synthesis. In this review, the underlying generation mechanisms and characteristics of influenza virus DIPs are summarized. We also discuss the potential impact of DIPs on the immunogenicity of live attenuated influenza vaccines (LAIVs) and development of influenza vaccines based on NS1 gene-defective DIPs. Finally, we review the antiviral strategies based on influenza virus DIPs that have been used against both influenza virus and SARS-CoV-2. This review provides systematic insights into the theory and application of influenza virus DIPs.

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Section: Potential Impact Of Dips On Immunogenicity Of Laivssupporting

confidence: 53%

Section: Immune Activation and Underlying Mechanisms Of Influenza Vir...mentioning

confidence: 99%

Section: Potential Impact Of Dips On Immunogenicity Of Laivsmentioning

confidence: 99%

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Defective Interfering Particles of Influenza Virus and Their Characteristics, Impacts, and Use in Vaccines and Antiviral Strategies: A Systematic Review

Zhou

Sheng

et al. 2022

Viruses

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“…Vaccination then promotes a cascade of miRNAs modified by that context which then leads to up- and down-regulation of genes and production of various interferons. Interferons play a critical role in the regulation of immune function [ 312 ], and even re-activate dormant persistent pathogens.…”

Section: System Complexity and The Unanticipated Effects Of Influenza...mentioning

confidence: 99%

Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths

Jones¹,

Ponomarenko

2022

Infectious Disease Reports

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Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes of infection by another. With up to 3000 species of human pathogens the potential combinations are vast. These combinations operate within further immune complexity induced by infection with multiple persistent pathogens, and by the role which the human microbiome plays in maintaining health, immune function, and resistance to infection. All the above are further complicated by malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for elderly individuals subsequently infected with influenza. However, all vaccines induce both specific and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity, while the nonspecific effects are far more nuanced including changes in gene expression patterns and production of small RNAs which contribute to pathogen interference. Little is known about the outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple other non-influenza winter pathogens. In this review we propose that in certain years the specific antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that the timing of vaccination relative to the pathogen balance was critical to success, was proposed in 2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza deaths are discussed.

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“…LAIVs. Additionally, LAIVs overall have been shown to produce large amounts of defectiveinterfering viral RNAs as a way to reduce infectivity, but this alone does not drive the reduction in vaccine effectiveness [24,25,36]. Taken together, our data suggests that the HA segment chosen for H1N1 LAIVs is an important determinant of innate immune induction, viral replication and perhaps subsequent vaccine efficacy.…”

Section: Discussionmentioning

confidence: 83%

HA and M2 sequences alter the replication of 2013-16 H1 Live Attenuated Influenza Vaccine Infection in Human Nasal Epithelial Cell cultures

Canaday

Resnick

Liu

et al. 2021

Preprint

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From 2013-2016, the H1N1 component of live, attenuated influenza vaccine (LAIV) performed very poorly in contrast to the inactivated influenza vaccine. We utilized a primary, differentiated human nasal epithelial (hNEC) culture system to assess the replication differences between isogenic LAIVs containing the HA segment from either A/Bolivia/559/2013 (rBol), which showed poor vaccine efficacy, and A/Slovenia/2903/2015 (rSlov), which had restored reasonable vaccine efficacy. While there were minimal differences in infectious virus production in Madin-Darby Canine Kidney (MDCK) cells, the rSlov LAIV showed markedly improved replication in hNEC cultures at both 32°C and 37°C, demonstrating that the HA segment alone could impact LAIV replication. The rSlov-infected hNEC cultures showed stronger production of interferon and proinflammatory chemokines which might also be contributing to the increased overall vaccine effectiveness of the rSlov LAIV through enhanced recruitment and activation of immune cells. The introduction of an M2-S86A mutation had no positive effects on H1 LAIV replication in hNEC cultures, in contrast to the increased infectious virus production seen with that mutation in an H3 LAIV. No obvious defects in viral RNA packaging were detected, suggesting the HA function may be driving the differential infectious virus production in hNEC cultures. The use of physiologically relevant temperatures and primary cell cultures demonstrated that candidate LAIVs can replicate efficiently, which is a necessary property for effective vaccines.

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Presence of defective viral genes in H1N1 live attenuated influenza vaccine strains is not associated with reduced human cell fitness or vaccine effectiveness

Cited by 5 publications

References 39 publications

Defective Interfering Particles of Influenza Virus and Their Characteristics, Impacts, and Use in Vaccines and Antiviral Strategies: A Systematic Review

Defective Interfering Particles of Influenza Virus and Their Characteristics, Impacts, and Use in Vaccines and Antiviral Strategies: A Systematic Review

Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths

HA and M2 sequences alter the replication of 2013-16 H1 Live Attenuated Influenza Vaccine Infection in Human Nasal Epithelial Cell cultures

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