scholarly journals Optimization of the Predicting of the Influenza Vaccine Strains

2019 ◽  
Vol 18 (1) ◽  
pp. 4-17 ◽  
Author(s):  
E. P. Kharchenko

 Relevance. Vaccination is still the most effective way to reduce the incidence and mortality from influenza and the complications it causes. WHO recommends the composition of the vaccine strain for each influenza season. Unfortunately, the relevance of vaccines and strains of influenza virus circulating during the epidemic season cannot always coincide. The cause is flu variability.Aim is to develop a new computational method for predicting an optimal hemagglutinin (HA) structure in H1N1 and H3N2 human influenza vaccine strains for coming epidemic seasons and to compare its results with WHO recommendations.Materials and method. For this study HA sequences were used from data bases available in INTERNET and the modified hidden Markov model was used to construct the HA primary structures.Results. It was indicated that the new bioinformatics approach allowed to construct an optimal structure of HA for vaccine strains. It was at most close to HA of circulating virus strains in coming epidemic seasons, spreaded over them and was superior to WHO recommendations. Conclusion: HA sequences should be considered as reliable background for predicting vaccine strains to decrease risks of not optimal and even mistakable choices. Bioinformatics approach allows to continually monitor HA changes after epidemics and to estimate adequacy of manufacturing vaccines to the future epidemic season.

2009 ◽  
Vol 14 (3) ◽  
Author(s):  
N Goddard ◽  
P Zucs ◽  
B Ciancio ◽  
F Plata ◽  
O Hungnes ◽  
...  

The influenza season 2008-9 started in week 49 of 2008 and is so far characterised by influenza virus type A subtype H3N2. Isolates of this subtype that were tested proved susceptible to neuraminidase inhibitors, but resistant to M2 inhibitors. The circulating A(H3N2) viruses are antigenically similar to the component in the current northern hemisphere influenza vaccine.


2019 ◽  
Vol 147 ◽  
Author(s):  
Lin-Lei Chen ◽  
Wai-Lan Wu ◽  
Wan-Mui Chan ◽  
Carol H. Y. Fong ◽  
Anthony C. K. Ng ◽  
...  

Abstract Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.


mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Hailiang Sun ◽  
Jialiang Yang ◽  
Tong Zhang ◽  
Li-Ping Long ◽  
Kun Jia ◽  
...  

ABSTRACTThe efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. As such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. Empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. Here, we present a novel, experimentally validated, computational method for determining influenza virus antigenicity on the basis of hemagglutinin (HA) sequence. This method integrates a bootstrapped ridge regression with antigenic mapping to quantify antigenic distances by using influenza HA1 sequences. Our method was applied to H3N2 seasonal influenza viruses and identified the 13 previously recognized H3N2 antigenic clusters and the antigenic drift event of 2009 that led to a change of the H3N2 vaccine strain.IMPORTANCEThis report supplies a novel method for quantifying antigenic distance and identifying antigenic variants using sequences alone. This method will be useful in influenza vaccine strain selection by significantly reducing the human labor efforts for serological characterization and will increase the likelihood of correct influenza vaccine candidate selection.


2015 ◽  
Vol 89 (6) ◽  
pp. 3308-3317 ◽  
Author(s):  
Sarah F. Andrews ◽  
Kaval Kaur ◽  
Noel T. Pauli ◽  
Min Huang ◽  
Yunping Huang ◽  
...  

ABSTRACTReactivation of memory B cells allows for a rapid and robust immune response upon challenge with the same antigen. Variant influenza virus strains generated through antigenic shift or drift are encountered multiple times over the lifetime of an individual. One might predict, then, that upon vaccination with the trivalent influenza vaccine across multiple years, the antibody response would become more and more dominant toward strains consistently present in the vaccine at the expense of more divergent strains. However, when we analyzed the vaccine-induced plasmablast, memory, and serological responses to the trivalent influenza vaccine between 2006 and 2013, we found that the B cell response was most robust against more divergent strains. Overall, the antibody response was highest when one or more strains contained in the vaccine varied from year to year. This suggests that in the broader immunological context of viral antigen exposure, the B cell response to variant influenza virus strains is not dictated by the composition of the memory B cell precursor pool. The outcome is instead a diversified B cell response.IMPORTANCEVaccine strategies are being designed to boost broadly reactive B cells present in the memory repertoire to provide universal protection to the influenza virus. It is important to understand how past exposure to influenza virus strains affects the response to subsequent immunizations. The viral epitopes targeted by B cells responding to the vaccine may be a direct reflection of the B cell memory specificities abundant in the preexisting immune repertoire, or other factors may influence the vaccine response. Here, we demonstrate that high preexisting serological antibody levels to a given influenza virus strain correlate with low production of antibody-secreting cells and memory B cells recognizing that strain upon revaccination. In contrast, introduction of antigenically novel strains generates a robust B cell response. Thus, both the preexisting memory B cell repertoire and serological antibody levels must be taken into consideration in predicting the quality of the B cell response to new prime-boost vaccine strategies.


2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Nicole Darricarrère ◽  
Svetlana Pougatcheva ◽  
Xiaochu Duan ◽  
Rebecca S. Rudicell ◽  
Te-Hui Chou ◽  
...  

ABSTRACT The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine. IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses.


2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Marten Heeringa ◽  
Brett Leav ◽  
Igor Smolenov ◽  
Giuseppe Palladino ◽  
Leah Isakov ◽  
...  

ABSTRACT We compared titers of antibodies against A/H1N1, A/H3N2, and B influenza virus strains collected pre- and postvaccination using hemagglutination inhibition (HI) and microneutralization (MN) assays and data from two vaccine trials: study 1, performed with a cell-grown trivalent influenza vaccine (TIVc) using cell-grown target virus in both assays, and study 2, performed with an egg-grown adjuvanted quadrivalent influenza vaccine (aQIVe) using egg-grown target virus. The relationships between HI- and MN-derived log-transformed titers were examined using different statistical techniques. Deming regression analyses showed point estimates for slopes generally close to 1 across studies and strains. The slope of regression was closest to 1 for A/H3N2 strain when either cell- or egg-grown viral target virus was used. Bland-Altman plots indicated a very small percentage of results outside 2 and 3 standard deviations. The magnitudes and directions of differences between titers in the two assays varied by study and strain. Mean differences favored the MN assay for A/H1N1 and B strains in study 1, whereas the titers determined by HI were higher than those determined by MN against the A/H3N2 strain. In study 2, mean differences favored the MN assay for A/H3N2 and B strains. Overall, the directions and magnitudes of the mean differences were similar between the two vaccines. The concordance correlation coefficient values ranged from 0.74 (A/H1N1 strain, study 1) to 0.97 (A/H3N2 strain, study 1). The comparative analysis demonstrates an overall strong positive correlation between the HI and MN assays. These data support the use of the MN assay to quantify the immune response of influenza vaccines in clinical studies, particularly for the A/H3N2 strain.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 973
Author(s):  
Quyen-Thi Nguyen ◽  
Young-Ki Choi

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.


2000 ◽  
Vol 38 (9) ◽  
pp. 3467-3469 ◽  
Author(s):  
Naoko Nakagawa ◽  
Ritsuko Kubota ◽  
Akiko Maeda ◽  
Toshimasa Nakagawa ◽  
Yoshinobu Okuno

Seventy-three B/Victoria group strains isolated in the 1996–1997 influenza season were divided into three groups according to the degree of reactivity to monoclonal antibody 8E6. Analysis of nucleotide sequences of the HA1 region clarified that single amino acid substitutions were responsible for the difference in reactivity to 8E6.


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 257
Author(s):  
Brianna L. Bullard ◽  
Eric A. Weaver

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to include strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and immunogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development of a universal influenza vaccine.


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