scholarly journals Passage Adaptation Correlates With the Reduced Efficacy of the Influenza Vaccine

2018 ◽  
Vol 69 (7) ◽  
pp. 1198-1204 ◽  
Author(s):  
Hui Chen ◽  
Jacob Josiah Santiago Alvarez ◽  
Sock Hoon Ng ◽  
Rasmus Nielsen ◽  
Weiwei Zhai
Keyword(s):  
Vaccine Efficacy ◽  
Probabilistic Method ◽  
Antigenic Drift ◽  
Darwinian Evolution ◽  
H3n2 Virus ◽  
Effective Vaccine ◽  
Sequence Evolution ◽  
Strong Negative Correlation ◽  
H3n2 Vaccine ◽  
Mutational Mapping

Abstract Background As a dominant seasonal influenza virus, H3N2 virus rapidly evolves in humans and is a constant threat to public health. Despite sustained research efforts, the efficacy of H3N2 vaccine has decreased rapidly. Even though antigenic drift and passage adaptation (substitutions accumulated during vaccine production in embryonated eggs) have been implicated in reduced vaccine efficacy (VE), their respective contributions to the phenomenon remain controversial. Methods We utilized mutational mapping, a powerful probabilistic method for studying sequence evolution, to analyze patterns of substitutions in different passage conditions for an unprecedented amount of H3N2 hemagglutinin sequences (n = 32 278). Results We found that passage adaptation in embryonated eggs is driven by repeated convergent evolution over 12 codons. Based on substitution patterns at these sites, we developed a metric, adaptive distance (AD), to quantify the strength of passage adaptation and subsequently identified a strong negative correlation between AD and VE. Conclusions The high correlation between AD and VE implies that passage adaptation in embryonated eggs may be a strong contributor to the recent reduction in H3N2 VE. We developed a computational package called MADE (Measuring Adaptive Distance and vaccine Efficacy based on allelic barcodes) to measure the strength of passage adaptation and predict the efficacy of a candidate vaccine strain. Our findings shed light on strategies for reducing Darwinian evolution within the passaging medium in order to potentially restore an effective vaccine program in the future.

scholarly journals Intention to Be Vaccinated for COVID-19 among Italian Nurses during the Pandemic

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 500
Author(s):  
Marco Trabucco Aurilio ◽  
Francesco Saverio Mennini ◽  
Simone Gazzillo ◽  
Laura Massini ◽  
Matteo Bolcato ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Online Survey ◽  
Vaccine Development ◽  
Vaccine Coverage ◽  
World Health ◽  
Vaccine Hesitancy ◽  
Effective Vaccine ◽  
Online Questionnaire ◽  
Cross Sectional ◽  
Female Sex

Background: While the COVID-19 pandemic has spread globally, health systems are overwhelmed by both direct and indirect mortality from other treatable conditions. COVID-19 vaccination was crucial to preventing and eliminating the disease, so vaccine development for COVID-19 was fast-tracked worldwide. Despite the fact that vaccination is commonly recognized as the most effective approach, according to the World Health Organization (WHO), vaccine hesitancy is a global health issue. Methods: We conducted a cross-sectional online survey of nurses in four different regions in Italy between 20 and 28 December 2020 to obtain data on the acceptance of the upcoming COVID-19 vaccination in order to plan specific interventions to increase the rate of vaccine coverage. Results: A total of 531 out of the 5000 nurses invited completed the online questionnaire. Most of the nurses enrolled in the study (73.4%) were female. Among the nurses, 91.5% intended to accept vaccination, whereas 2.3% were opposed and 6.2% were undecided. Female sex and confidence in vaccine efficacy represent the main predictors of vaccine intention among the study population using a logistic regression model, while other factors including vaccine safety concerns (side effects) were non-significant. Conclusions: Despite the availability of a safe and effective vaccine, intention to be vaccinated was suboptimal among nurses in our sample. We also found a significant number of people undecided as to whether to accept the vaccine. Contrary to expectations, concerns about the safety of the vaccine were not found to affect the acceptance rate; nurses’ perception of vaccine efficacy and female sex were the main influencing factors on attitudes toward vaccination in our sample. Since the success of the COVID-19 immunization plan depends on the uptake rate, these findings are of great interest for public health policies. Interventions aimed at increasing employee awareness of vaccination efficacy should be promoted among nurses in order to increase the number of vaccinated people.

scholarly journals Prediction of vaccine efficacy of the Delta variant

2021 ◽  
Author(s):  
Xinhua Chen ◽  
Andrew S. Azman ◽  
Wanying Lu ◽  
Ruijia Sun ◽  
Nan Zheng ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Protective Efficacy ◽  
Adenovirus Vector ◽  
Neutralizing Antibody ◽  
Effective Vaccine ◽  
Public Health Decision ◽  
Additional Tool ◽  
Health Decision Making ◽  
Health Decision ◽  
Antibody Titers

AbstractThe emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.

scholarly journals Genotype patterns of contemporary reassorted H3N2 virus in US swine

2013 ◽  
Vol 94 (6) ◽  
pp. 1236-1241 ◽  
Author(s):  
Pravina Kitikoon ◽  
Martha I. Nelson ◽  
Mary Lea Killian ◽  
Tavis K. Anderson ◽  
Leo Koster ◽  
...  
Keyword(s):  
North American ◽  
Swine Influenza ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
H3n2 Virus ◽  
Specific Subset ◽  
The Usa ◽  
Genome Scale ◽  
Viral Isolates

To understand the evolution of swine-origin H3N2v influenza viruses that have infected 320 humans in the USA since August 2011, we performed a phylogenetic analysis at a whole genome scale of North American swine influenza viruses (n  =  200). All viral isolates evolved from the prototypical North American H3 cluster 4 (c4), with evidence for further diversification into subclusters. At least ten distinct reassorted H3N2/pandemic H1N1 (rH3N2p) genotypes were identified in swine. Genotype 1 (G1) was most frequently detected in swine and all human H3N2v viruses clustered within a single G1 clade. These data suggest that the genetic requirements for transmission to humans may be restricted to a specific subset of swine viruses. Mutations at putative antigenic sites as well as reduced serological cross-reactivity among the H3 subclusters suggest antigenic drift of these contemporary viruses.

scholarly journals SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses

2021 ◽  
Author(s):  
Debashree Chatterjee ◽  
Alexandra Tauzin ◽  
Lorie Marchitto ◽  
Shang Yu Gong ◽  
Marianne Boutin ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Vaccine Efficacy ◽  
Short Interval ◽  
Antigenic Drift ◽  
Alpha Beta ◽  
Induced Immunity ◽  
Plasma Activity

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

scholarly journals Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yiquan Wang ◽  
Ruipeng Lei ◽  
Armita Nourmohammad ◽  
Nicholas C Wu
Keyword(s):  
Fitness Landscape ◽  
H3n2 Virus ◽  
Effective Vaccine ◽  
Net Charge ◽  
Antigenic Region ◽  
Immune Pressure ◽  
Antigenic Evolution ◽  
Combinatorial Mutagenesis ◽  
Charge Balancing ◽  
Generation Sequencing

As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has recently emerged as an effective vaccine target, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply combinatorial mutagenesis and next-generation sequencing to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region is correlated with the pairwise epistasis between charge states. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a model of influenza evolution.

scholarly journals Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

2020 ◽  
Author(s):  
John Huddleston ◽  
John R. Barnes ◽  
Thomas Rowe ◽  
Xiyan Xu ◽  
Rebecca Kondor ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Adaptive Immunity ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Antigenic Drift ◽  
Functional Constraint ◽  
Effective Vaccine ◽  
Experimental Measurements ◽  
One Year

AbstractSeasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

scholarly journals 2556. Retrospective Evaluation of Mismatch From Egg-Based Isolation of Influenza Strains Compared With Cell-Based Isolation and the Possible Implications for Vaccine Effectiveness

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S69-S69 ◽  
Author(s):  
S Rajaram ◽  
Josephine Van Boxmeer ◽  
Brett Leav ◽  
Pirada Suphaphiphat ◽  
Ike Iheanacho ◽  
...  
Keyword(s):  
Mdck Cells ◽  
Glycosylation Site ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Wild Type Virus ◽  
Wild Type ◽  
Research Support ◽  
Antigenic Similarity ◽  
H3n2 Vaccine

Abstract Background Lower influenza vaccine effectiveness (VE) against circulating H3N2 strains compared with other influenza viruses is partly explained by antigenic mismatch between circulating strains and the vaccine strain (Belongia 2016). This mismatch has recently been linked to a new glycosylation site introduced in the egg-adaptation step (Zost 2017) and HA L194P substitution (Wu 2017) for H3N2. Vaccine manufactured using seed virus wholly grown in mammalian (e.g., Madin–Darby Canine Kidney—MDCK) cells, as with the NH17-18 version of Flucelvax®, avoids these mutations. Preliminary reports suggest that this cell-based vaccine showed greater VE than did similar egg-based vaccines [FDA Statement]. This study aimed to compile existing data on antigenic similarity to measure the degree of match with circulating wild-type isolates of egg- and MDCK-propagated versions of the vaccine H3N2 virus over multiple seasons. Methods Using publicly available reports from the Worldwide Influenza Centre, London (Crick), we compiled data on antigenic similarity, defined as H3N2 circulating wild-type virus isolates showing no more than a 4-fold reduction in titer to antisera raised against wholly MDCK- or egg-propagated versions of the vaccine H3N2 viruses. Titers were compared using hemagglutination inhibition (HI) assays and/or plaque reduction neutralization assays (PRNA). Results Data from Northern Hemisphere influenza seasons of 2011–2012 to 2017–2018 show a substantially higher proportion of tested circulating influenza H3N2 viruses matched the MDCK-propagated reference viruses than did corresponding egg-propagated reference vaccine viruses (Figures 1 and 2). In half of the seasons evaluated, there was little to no antigenic similarity between circulating viruses and the egg-based vaccine viral seed. Conclusion These data suggest higher levels of mismatch have occurred consistently with egg-propagated H3N2 reference viruses compared with MDCK-propagated reference viruses when measured against circulating wild-type isolates and may further explain the potential for lower VE observed against H3N2 historically. Furthermore, these data point to the importance of continuing to utilize cell-derived seeds in creating seasonal influenza vaccines for this strain. Disclosures S. Rajaram, Seqirus: Employee, Salary. J. Van Boxmeer, Seqirus: Employee, Salary. B. Leav, Seqirus: Employee and Shareholder, Salary. P. Suphaphiphat, Seqirus: Employee, Salary. I. Iheanacho, Seqirus: Consultant, Research support. K. Kistler, Seqirus: Consultant, Research support.

scholarly journals Antigenic analysis of prototype influenza A (H3N2) strains by the antiserum absorption method

1973 ◽  
Vol 71 (3) ◽  
pp. 501-508 ◽  
Author(s):  
Gy. Tak´tsy ◽  
K. Barb
Keyword(s):  
Influenza A ◽  
Antigenic Drift ◽  
H3n2 Virus ◽  
Absorption Test ◽  
Absorption Method ◽  
Antigenic Analysis

SUMMARYPrototype strains of the influenza A (H3N2) virus can be arranged on a gradient showing the degree of the antigenic drift which the haemagglutinins of the strains have undergone. The demonstration of fine antigenic differences is based on an antiserum absorption test which allows a detailed antigenic analysis of strains. The gradient provides information on variation in strains occurring in different geographical areas and its use may be helpful in differentiating between introduced strains and locally developing variants.

scholarly journals Recent Human Influenza A/H3N2 Virus Evolution Driven by Novel Selection Factors in Addition to Antigenic Drift

2009 ◽  
Vol 200 (8) ◽  
pp. 1232-1241 ◽  
Author(s):  
Matthew J. Memoli ◽  
Brett W. Jagger ◽  
Vivien G. Dugan ◽  
Li Qi ◽  
Jadon P. Jackson ◽  
...  
Keyword(s):  
Influenza A ◽  
Virus Evolution ◽  
Antigenic Drift ◽  
H3n2 Virus ◽  
Human Influenza ◽  
Selection Factors

scholarly journals Serological studies of influenza viruses in pigs in Great Britain 1991–2

1995 ◽  
Vol 114 (3) ◽  
pp. 511-520 ◽  
Author(s):  
I. H. Brown ◽  
P. A. Harris ◽  
D. J. Alexander
Keyword(s):  
Great Britain ◽  
Influenza A ◽  
H1n1 Virus ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
H3n2 Virus ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza A Viruses

SUMMARYSamples from a sow serum bank representative of the pig population of Great Britain collected during 1991–2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of ‘classical swine’ H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination-inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9·9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza.

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