Impact of Influenza B Lineage-Level Mismatch Between Trivalent Seasonal Influenza Vaccines and Circulating Viruses, 1999–2012

Seasonal influenza vaccines are often ineffective because they elicit strain-specific antibody responses to mutation-prone sites on the hemagglutinin (HA) head. Vaccines that provide long-lasting immunity to conserved epitopes are needed. Recently, we reported a nanoparticle-based vaccine platform produced by solid-phase peptide synthesis (SPPS) for targeting linear and helical protein-based epitopes. Here, we illustrate its potential for building broadly protective influenza vaccines. Targeting known epitopes in the HA stem, neuraminidase (NA) active site, and M2 ectodomain (M2e) conferred 50–75% survival against 5LD50 influenza B and H1N1 challenge; combining stem and M2e antigens increased survival to 90%. Additionally, protein sequence and structural information were employed in tandem to identify alternative epitopes that stimulate greater protection; we report three novel HA and NA sites that are highly conserved in type B viruses. One new target in the HA stem stimulated 100% survival, highlighting the value of this simple epitope discovery strategy. A candidate influenza B vaccine targeting two adjacent HA stem sites led to >104-fold reduction in pulmonary viral load. These studies describe a compelling platform for building vaccines that target conserved influenza epitopes.

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A Reduced-Dose Seasonal Trivalent Influenza Vaccine Is Safe and Immunogenic in Adult and Elderly Patients in a Randomized Controlled Trial

Clinical and Vaccine Immunology ◽

10.1128/cvi.05619-11 ◽

2012 ◽

Vol 19 (3) ◽

pp. 313-318 ◽

Cited By ~ 5

Author(s):

Zoltan Vajo ◽

Ferenc Tamas ◽

Istvan Jankovics

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

Seasonal Influenza ◽

Geometric Mean ◽

Influenza Vaccines ◽

Elderly Subjects ◽

Influenza B Virus ◽

Influenza B ◽

Reduced Dose ◽

Influenza A H1n1

ABSTRACTWith the recent pandemic of influenza A (H1N1) and vaccine shortages, there has been considerable interest in developing influenza vaccines with reduced doses, allowing for increased production capacity. Here we report a prospective, randomized, double-blind, single-center clinical trial of a reduced-dose whole-virion inactivated, adjuvanted influenza vaccine in adult and elderly volunteers. A total of 234 subjects, including 120 adults (18 to 60 years of age) and 114 elderly subjects (>60 years of age) were enrolled to receive either 6 μg or the conventional 15-μg dose of seasonal trivalent influenza vaccines. The subjects were followed for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition testing. The subjects developed antibody responses against the seasonal influenza A virus H1N1 and H3N2 strains, as well as the seasonal influenza B virus included in the vaccines. Single doses of 6 μg fulfilled licensing criteria for seasonal influenza vaccines. No significant differences in rates of seroconversion or seroprotection or in geometric mean titers were found between the two dosage levels. All adverse events were rare, mild, and transient. We found that the present reduced-dose vaccine is safe and immunogenic in healthy adult and elderly subjects and triggers immune responses that comply with licensing criteria.

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Debate on the compositions of influenza B in northern hemisphere seasonal influenza vaccines

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-019-0631-2 ◽

2019 ◽

Vol 8 (1) ◽

Author(s):

Guozhong He ◽

Pengfei Yang ◽

Qingli Yan ◽

Chenglong Xiong

Keyword(s):

Northern Hemisphere ◽

Influenza A ◽

Phylogenetic Trees ◽

Seasonal Influenza ◽

Genetic Distances ◽

Influenza Vaccines ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A H1n1 ◽

The Mean

Abstract Background Annual influenza vaccination is the most effective way to prevent influenza. Influenza vaccines have traditionally included the hemagglutinins (HA) and neuraminidases (NA) from the two A viruses (H1N1 and H3N2) and either B Yamagata or B Victoria. Mismatches between circulating isolates of influenza B and the vaccines are very common. Taking 2017/2018 winter in northern hemisphere as an example, this study was designed to find out the reasons for mismatch between the trivalent influenza vaccine (TIV) and most of the epidemic isolates at that time, and to discuss if there are some optimized programs for seasonal influenza vaccines. Methods HA and NA sequences of the seasonal isolates circulating from December 1, 2017 to February 28, 2018, and in the previously other 7 winters in northern hemisphere from Global Initiative on Sharing All Influenza Data (GISAID) and the influenza database of National Center for Biotechnology Information (NCBI). Phylogenetic trees and genetic distances were constructed or calculated by using MAFFT and MEGA 6.0 software. Results Influenza B composition in the TIV recommendation mismatched most of circulating viruses in 2017/2018 winter; the vaccine strain was from the B/Victoria lineage, while most of epidemic isolates were from the B/Yamagata lineage. The epidemic lineage of influenza B reached its peak a little late in the previous winter might be responsible for this mismatch. During 2010–2018, the mean genetic distances between epidemic isolates of influenza A (H1N1 and H3N2) and the vaccines were no higher than 0.02375 ± 0.00341 in both HA and NA. However, concerning influenza B virus, when forecasting done well, the mean genetic distances between epidemic isolates and the vaccines were no higher than 0.02368 ± 0.00272; otherwise, the distances could reach 0.13695 ± 0.00238. Conclusion When applying quadrivalent influenza vaccines (QIVs) for vaccination, the recommendations of compositions for influenza B could be altered and assessed once in 3 or 4 years; when economic burden was considered intensively and TIVs were utilized, the recommended compositions for influenza B could be announced in April or May, rather than in February or March as now.

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Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011–2012 to 2016–2017

Clinical Infectious Diseases ◽

10.1093/cid/ciaa102 ◽

2020 ◽

Cited By ~ 4

Author(s):

Manjusha Gaglani ◽

Anupama Vasudevan ◽

Chandni Raiyani ◽

Kempapura Murthy ◽

Wencong Chen ◽

...

Keyword(s):

United States ◽

Cost Benefit ◽

Health Impact ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Vaccines ◽

Influenza B ◽

Illness Onset ◽

Inactivated Vaccines ◽

B Lineage

Abstract Background Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. Methods The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011–2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013–2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. Results Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45–59) for IIV4 versus 45% (95% CI, 34–54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. Conclusions The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

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Influenza B Lineages Have More in Common Than Meets the Eye. Trivalent Influenza Vaccines Trigger Heterotypic Antibodies Against Both Influenza B Viruses

Frontiers in Microbiology ◽

10.3389/fmicb.2021.737216 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura Sánchez-de Prada ◽

Silvia Rojo-Rello ◽

Marta Domínguez-Gil ◽

Eduardo Tamayo-Gómez ◽

Raúl Ortiz de Lejarazu-Leonardo ◽

...

Keyword(s):

Influenza Vaccine ◽

Seasonal Influenza ◽

The Elderly ◽

Cross Reactivity ◽

Influenza Vaccines ◽

Influenza B ◽

Relevant Factor ◽

Serum Samples ◽

Trivalent Influenza Vaccine ◽

Before And After

Influenza B is accountable for an important burden during flu epidemics, causing special impact in children and the elderly. Vaccination is the best approach to address influenza infections. However, one of the main problems of this virus is that two different lineages circulate together, Victoria and Yamagata; and trivalent vaccines, that only contain one of these lineages, are still in use. For that reason, if during an epidemic, the lineage not included in the vaccine predominates, a mismatch would occur, and the vaccine effectiveness will be very poor. In this work, we evaluated the cross-protection given by the trivalent Influenza vaccine and compared serological profiles based on age, sex, and the type of vaccine used. We performed a retrospective analysis of serum samples obtained before and after seasonal influenza vaccination during 20 seasons (1998–2018). The results showed that heterotypic reactivity between both influenza B lineages is common, but always lower than the homologous response. Age is a relevant factor for this cross-reactivity between both lineages, while the sex and the type of vaccine not. Vaccination with trivalent influenza vaccines elicits cross-reactive antibodies against both lineages, however, this response might not be enough to provide an appropriate serological protection in case of mismatch.

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B Cell and Antibody Response to Seasonal Influenza Vaccines in Younger and Older Adults

Case Medical Research ◽

10.31525/ct1-nct04101838 ◽

2019 ◽

Author(s):

Keyword(s):

Older Adults ◽

Antibody Response ◽

B Cell ◽

Seasonal Influenza ◽

Influenza Vaccines

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Willingness to Receive the COVID-19 and Seasonal Influenza Vaccines among the Saudi Population and Vaccine Uptake During the Initial Stage of the National Vaccination Campaign: A Cross-Sectional Survey

Vaccines ◽

10.3390/vaccines9070765 ◽

2021 ◽

Vol 9 (7) ◽

pp. 765

Author(s):

Amel Ahmed Fayed ◽

Abeer Salem Al Shahrani ◽

Leenah Tawfiq Almanea ◽

Nardeen Ibrahim Alsweed ◽

Layla Mohammed Almarzoug ◽

...

Keyword(s):

Saudi Arabia ◽

Perceived Risk ◽

Online Survey ◽

Seasonal Influenza ◽

Vaccination Campaign ◽

Vaccine Uptake ◽

Influenza Vaccines ◽

Vaccine Hesitancy ◽

Cross Sectional ◽

To Receive

This study aimed to assess the willingness to receive the coronavirus disease 2019 (COVID-19) and seasonal influenza vaccines and vaccine uptake during the early stage of the national vaccination campaign in Saudi Arabia. A cross-sectional online survey was conducted among adult Saudis between 20 January and 20 March 2021. The questionnaire addressed vaccine hesitancy, perceived risk, willingness, and vaccine uptake. Approximately 39% of the participants expressed vaccine hesitancy, and 29.8% and 24% felt highly vulnerable to contracting COVID-19 and seasonal influenza, respectively. The majority (59.5%) were willing to receive the COVID-19 vaccine, although only 31.7% were willing to receive the flu vaccine. Adjusted analysis showed that vaccine hesitancy (OR 0.34, 95% CI 0.27–0.43) and the perception of being at high risk (OR 2.78, 95% CI 1.68–4.60) independently affected the intention to be vaccinated. Vaccine hesitancy was similar among those who were willing to be vaccinated (29.8%) and those who had already been vaccinated (33.1%). The perceived risk was significantly higher among those who had been vaccinated (48.1%) than among those who were willing to be vaccinated but had not yet been vaccinated (29.1%). In conclusion, the acceptance of the COVID-19 vaccine in Saudi Arabia is high. Saudis who received the vaccine had a similar level of vaccine hesitancy and a higher level of perceived risk.

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Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽

10.3390/v13060977 ◽

2021 ◽

Vol 13 (6) ◽

pp. 977

Author(s):

Kobporn Boonnak ◽

Chayasin Mansanguan ◽

Dennis Schuerch ◽

Usa Boonyuen ◽

Hatairat Lerdsamran ◽

...

Keyword(s):

Amino Acid ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Surface Proteins ◽

Antigenic Drift ◽

Influenza B ◽

Receptor Binding Site ◽

Antigenic Sites ◽

Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

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