Identification of Critical Residues in the Hemagglutinin and Neuraminidase of Influenza Virus H1N1pdm for Vaccine Virus Replication in Embryonated Chicken Eggs

Wang, Weijia; Lu, Janine; Cotter, Christopher R.; Wen, Katie; Jin, Hong; Chen, Zhongying

doi:10.1128/jvi.03271-12

Cited by 21 publications

(21 citation statements)

References 36 publications

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“…It has been reported that negatively charged residues in A(H1N1)pdm09 HA possibly decrease HA-sialic acid interaction and facilitate release of progeny for multiple cycle replication, which may increase the yield of virus [20]; however, in this study viruses with better yields had either a positively charged (I216R) or a hydrophobic (D187V) substitution. The two poorer yielding viruses had S190R, or an uncharged D187S substitution.…”

Section: Discussionmentioning

confidence: 73%

The Ability of a Non-Egg Adapted (Cell-Like) A(H1N1)pdm09 Virus to Egg-Adapt at HA Loci Other than 222 and 223 and Its Effect on the Yield of Viral Protein

et al. 2016

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Previous studies on influenza A(H1N1)pdm09 candidate vaccine viruses (CVVs) that had adapted to growth in embryonated chicken eggs by the acquisition of amino acid substitutions at HA positions 222 or 223 showed that improved protein yield could be conferred by additional amino acid substitutions in the haemagglutinin (HA) that arose naturally during passaging of the virus in eggs. In this study we investigated, by means of reverse genetics, the ability of a non-egg adapted (cell-like) A(H1N1)pdm09 virus to egg-adapt at HA loci other than 222/223, introducing amino acid substitutions previously identified as egg adaptations in pre-H1N1pdm09 H1N1 viruses and assessing their effect on protein yield and antigenicity. We also investigated the effect on the protein yield of these substitutions in viruses that had A(H1N1)pdm09 internal genes rather than the traditional PR8 internal genes of a CVV. The data show that a cell-like A/Christchurch/16/2010 can be egg-adapted via amino acid substitutions in at least three alternative HA loci (187, 190 and 216), in viruses with either PR8 or A/California/7/2009 internal genes, but that the effects on protein yield vary depending on the amino acid substitution and the internal genes of the virus. Since CVVs need to produce high protein yields to be suitable for vaccine manufacture, the findings of this study will assist in the future characterisation of both wild type viruses and lab-derived CVVs for vaccine use.

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Section: Discussionmentioning

confidence: 73%

The Ability of a Non-Egg Adapted (Cell-Like) A(H1N1)pdm09 Virus to Egg-Adapt at HA Loci Other than 222 and 223 and Its Effect on the Yield of Viral Protein

et al. 2016

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“…Similar to other swine‐origin influenza H1N1pdm 2009 viruses, Gil11 replicated poorly in both MDCK cells and eggs, reaching a peak titer of 10 5 TCID 50 /ml only . Gil11 was antigenically similar to CA09 as determined by serum HAI assay . CA09 can grow to high titer after egg adaptation and was therefore used to evaluate the morbidity caused by H1N1pdm infection in ferrets instead of Gil11 .…”

Section: Resultsmentioning

confidence: 97%

Influenza H1N1pdm‐specific maternal antibodies offer limited protection against wild‐type virus replication and influence influenza vaccination in ferrets

Suguitan¹,

Zengel²,

Jacobson³

et al. 2013

Influenza Resp Viruses

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ObjectiveThe objective was to study passively acquired influenza H1N1 pandemic (H1N1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the H1N1pdm.Design and main outcome measuresInfectivity of the H1N1pdm in the respiratory tract of ferrets was compared with the previous seasonal A/South Dakota/6/2007 (SD07, H1N1). Influenza-specific antibodies were quantitated and antibody-mediated protection against the homologous and heterologous H1N1 virus challenge infection was determined.ResultsH1N1pdm virus was approximately 10 times more infectious than SD07 in ferrets, replicated to higher viral titers in the upper respiratory tract and shed for a longer duration. Influenza-specific antibodies after natural infection persisted much longer in the circulation than passively acquired maternal antibodies. The protection conferred by the maternal antibodies was limited to the homologous virus strain and was ineffective against SD07 and H3N2 virus. Serum antibodies from maternal transmission or passive transfer interfered with homologous vaccine strain-mediated antibody responses in the ferret. A booster immunization was required to elicit a high level of antibody.ConclusionsThe findings support the rationale for a prime and boost immunization strategy in young children in whom maternal antibodies are present.

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“…A single dose provides complete protection against wt H7N9 and H7N7 challenge infection in ferrets. The HA residues identified in H1N1pdm and seasonal influenza viruses that improve vaccine virus growth in eggs are generally at or near the receptor binding site (RBS) (39)(40)(41). The changes identified in the H7N9 HA at residues 133,135,158,160,193,198,199,220, and 224 following egg and MDCK cell passage are also located in proximity to the RBS (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Similar changes were also identified in the HA of the H1N1pdm viruses, K122E, A189D, N128D, D130E, and K212E (H3#), that improved vaccine virus growth in eggs and MDCK cells. Further studies indicated that the acidic residue substitutions in H1N1pdm did not affect viral entry and replication but greatly improved viral spread in the host cells (41). These negatively charged residues possibly decrease the HA and sialic acid interaction and thus facilitate the release of progeny viruses from infected cells for efficient multicycle replication.…”

Section: Discussionmentioning

confidence: 99%

Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets

Chen

Baz

et al. 2014

J Virol

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IMPORTANCEIn response to the recent avian H7N9 influenza virus infection in humans, we developed a live attenuated H7N9 influenza vaccine (LAIV) with two amino acid substitutions in the viral HA protein that improved vaccine yield by 10-fold in chicken embryonated eggs, the substrate for vaccine manufacture. The two amino acids also improved the antigen yield for inactivated H7N9 vaccines, demonstrating that this finding could great facilitate the efficiency of H7N9 vaccine manufacture. The candidate H7N9 LAIV was immunogenic and protected ferrets against homologous and heterologous wild-type H7 virus challenge, making it suitable for use in protecting humans from H7 infection.

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Identification of Critical Residues in the Hemagglutinin and Neuraminidase of Influenza Virus H1N1pdm for Vaccine Virus Replication in Embryonated Chicken Eggs

Cited by 21 publications

References 36 publications

The Ability of a Non-Egg Adapted (Cell-Like) A(H1N1)pdm09 Virus to Egg-Adapt at HA Loci Other than 222 and 223 and Its Effect on the Yield of Viral Protein

The Ability of a Non-Egg Adapted (Cell-Like) A(H1N1)pdm09 Virus to Egg-Adapt at HA Loci Other than 222 and 223 and Its Effect on the Yield of Viral Protein

Influenza H1N1pdm‐specific maternal antibodies offer limited protection against wild‐type virus replication and influence influenza vaccination in ferrets

Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets

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