Vaccines for Influenza

Tsilibary, Effie Photini C.; Charonis, Spyros; Georgopoulos, Apostolos P.

doi:10.3390/vaccines9010047

Cited by 9 publications

(10 citation statements)

References 16 publications

(27 reference statements)

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“…The HA, NA and matrix proteins provide a diverse set of highly conserved influenza virus epitopes that we incorporated into our composite influenza peptide immunogens. While HA has been a focus for many seasonal vaccines, other influenza proteins such as NA and M2e have been proposed as important vaccine components to induce broad neutralizing antibodies [ 5 , 6 , 7 , 8 , 9 , 10 ]. Monoclonal antibodies to each of the peptide epitopes in the composite antigens used in this study were shown to neutralize influenza viruses across Groups 1 and 2 contemporary strains (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…Immunity to influenza induced by M2e may include both innate and adaptive immune responses and therefore has been considered an important target for developing a universal influenza vaccine [ 8 , 9 ]. The HA and NA peptides are highly conserved and located near or at the protein area where the receptor binding sites reside [ 10 , 11 , 12 ]. These epitopes classically are impacted by induction of antibodies through the adaptive immune system and a major target for influenza vaccines.…”

Section: Introductionmentioning

confidence: 99%

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Conserved Influenza Hemagglutinin, Neuraminidase and Matrix Peptides Adjuvanted with ALFQ Induce Broadly Neutralizing Antibodies

Sei

Rao

Schuman³

et al. 2021

Vaccines

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A universal influenza candidate vaccine that targets multiple conserved influenza virus epitopes from hemagglutinin (HA), neuraminidase (NA) and matrix (M2e) proteins was combined with the potent Army liposomal adjuvant (ALFQ) to promote induction of broad immunity to seasonal and pandemic influenza strains. The unconjugated and CRM-conjugated composite peptides formulated with ALFQ were highly immunogenic and induced both humoral and cellular immune responses in mice. Broadly reactive serum antibodies were induced across various IgG isotypes. Mice immunized with the unconjugated composite peptide developed antibody responses earlier than mice immunized with conjugated peptides, and the IgG antibodies were broadly reactive and neutralizing across Groups 1 and 2 influenza viruses. Multi-epitope unconjugated influenza composite peptides formulated with ALFQ provide a novel strategy for the development of a universal influenza vaccine. These synthetic peptide vaccines avoid the pitfalls of egg-produced influenza vaccines and production can be scaled up rapidly and economically.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conserved Influenza Hemagglutinin, Neuraminidase and Matrix Peptides Adjuvanted with ALFQ Induce Broadly Neutralizing Antibodies

Sei

Rao

Schuman³

et al. 2021

Vaccines

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“…Improvements in influenza vaccine technology such as cell versus egg grown vaccines, adjuvants, etc [123,124].…”

Section: Factors Increasing Ewm With Time Factors Reducing Ewm With Timementioning

confidence: 99%

Trends in Excess Winter Mortality (EWM) From 1900/01 to 2019/20—Evidence for a Complex System of Multiple Long-Term Trends

Jones¹,

Ponomarenko²

2022

Preprint

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Trends in excess winter mortality (EWM) were investigated from the winter of 1900/01 to 2019/20. During the 1918-1919 Spanish flu epidemic a maximum EWM of 100% was observed in both Denmark and the USA. During the Spanish flu epidemic in the USA 70% of excess winter deaths were coded to influenza. EWM steadily declined from the Spanish flu peak to a minimum around the 1970’s to 1980’s. There is evidence that this decline was accompanied by a shift in deaths away from the winter, and that the EWM calculation shifted from a maximum around April to June in the early 1900’s to around March since 1967. EWM has a good correlation with the number of estimated influenza deaths, but in this context influenza pandemics after the Spanish flu only had an EWM equivalent to that for seasonal influenza. Using data from 1980 onward the effect of influenza vaccination on EWM was examined using a large international data set. No effect of increasing influenza vaccination could be discerned; however, there are multiple competing forces influencing EWM which will obscure any underlying trend, e.g., increasing age at death, multimorbidity, dementia, polypharmacy, diabetes, and obesity – all of which either interfere with vaccine effectiveness or are risk factors for influenza death. After adjusting the trend in EWM in the USA influenza vaccination can be seen to be masking higher winter deaths among a high morbidity US population. Winter deaths are clearly the outcome of a complex system of competing long-term trends.

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“…Consequently, a number of research teams and pharma companies have carried out studies aimed at developing a universal vaccine against the influenza virus. There are different approaches to constructing a universal influenza vaccine, e.g., developing recombinant protein immunogens, using conserved influenza virus antigens (hemagglutinin stem, and proteins NP, PB1, M1, and M2), or developing new types of vaccines [ 1 , 2 , 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens

et al. 2021

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Nucleic acid-based influenza vaccines are a promising platform that have recently and rapidly developed. We previously demonstrated the immunogenicity of DNA vaccines encoding artificial immunogens AgH1, AgH3, and AgM2, which contained conserved fragments of the hemagglutinin stem of two subtypes of influenza A—H1N1 and H3N2—and conserved protein M2. Thus, the aim of this study was to design and characterize modified mRNA obtained using the above plasmid DNA vaccines as a template. To select the most promising protocol for creating highly immunogenic mRNA vaccines, we performed a comparative analysis of mRNA modifications aimed at increasing its translational activity and decreasing toxicity We used mRNA encoding a green fluorescent protein (GFP) as a model. Eight mRNA-GFP variants with different modifications (M0–M7) were obtained using the classic cap(1), its chemical analog ARCA (anti-reverse cap analog), pseudouridine (Ψ), N6-methyladenosine (m6A), and 5-methylcytosine (m5C) in different ratios. Modifications M2, M6, and M7, which provided the most intensive fluorescence of transfected HEK293FT cells were used for template synthesis when mRNA encoded influenza immunogens AgH1, AgH3, and AgM2. Virus specific antibodies were registered in groups of animals immunized with a mix of mRNAs encoding AgH1, AgH3, and AgM2, which contained either ARCA (with inclusions of 100% Ψ and 20% m6A (M6)) or a classic cap(1) (with 100% substitution of U with Ψ (M7)). M6 modification was the least toxic when compared with other mRNA variants. M6 and M7 RNA modifications can therefore be considered as promising protocols for designing mRNA vaccines.

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Vaccines for Influenza

Abstract: Two reviews by Harding and Heaton [...]

Cited by 9 publications

References 16 publications

Conserved Influenza Hemagglutinin, Neuraminidase and Matrix Peptides Adjuvanted with ALFQ Induce Broadly Neutralizing Antibodies

Conserved Influenza Hemagglutinin, Neuraminidase and Matrix Peptides Adjuvanted with ALFQ Induce Broadly Neutralizing Antibodies

Trends in Excess Winter Mortality (EWM) From 1900/01 to 2019/20—Evidence for a Complex System of Multiple Long-Term Trends

Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens

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