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3 pages, 186 KiB

Open AccessEditorial

Progress on Seasonal and Pandemic Influenza Vaccines

by Claudia Maria Trombetta and Emanuele Montomoli

Vaccines 2021, 9(10), 1068; https://doi.org/10.3390/vaccines9101068 - 24 Sep 2021

Cited by 2 | Viewed by 1482

Abstract

Influenza is a vaccine-preventable disease and vaccination is the most effective way of controlling seasonal influenza infections and preventing possible pandemic events [...] Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

Research

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12 pages, 1383 KiB

Open AccessArticle

Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

by Jongsuk Mo, Stivalis Cardenas-Garcia, Jefferson J. S. Santos, Lucas M. Ferreri, C. Joaquín Cáceres, Ginger Geiger, Daniel R. Perez and Daniela S. Rajao

Vaccines 2021, 9(7), 800; https://doi.org/10.3390/vaccines9070800 - 19 Jul 2021

Cited by 4 | Viewed by 2982

Abstract

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children, and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of an HA [...] Read more.

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children, and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of an HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation to stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations, along with attenuating mutations E580G and S660A, in PB1 of B/Bris (B/Bris PB1att 4M). Serial passages of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

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21 pages, 5775 KiB

Open AccessArticle

Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein

by C. Joaquín Cáceres, Stivalis Cardenas-Garcia, Aarti Jain, L. Claire Gay, Silvia Carnaccini, Brittany Seibert, Lucas M. Ferreri, Ginger Geiger, Algimantas Jasinskas, Rie Nakajima, Daniela S. Rajao, Irina Isakova-Sivak, Larisa Rudenko, Amy L. Vincent, D. Huw Davies and Daniel R. Perez

Vaccines 2021, 9(7), 703; https://doi.org/10.3390/vaccines9070703 - 27 Jun 2021

Cited by 9 | Viewed by 3391

Abstract

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) [...] Read more.

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, the introduction of genes encoding immunomodulatory functions into a candidate LAIV can serve as natural adjuvants to improve overall vaccine safety and efficacy. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

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17 pages, 2595 KiB

Open AccessArticle

Quantifying the Persistence of Vaccine-Related T Cell Epitopes in Circulating Swine Influenza A Strains from 2013–2017

by Swan Tan, Andres Hazaet Gutiérrez, Phillip Charles Gauger, Tanja Opriessnig, Justin Bahl, Leonard Moise and Anne Searls De Groot

Vaccines 2021, 9(5), 468; https://doi.org/10.3390/vaccines9050468 - 6 May 2021

Cited by 3 | Viewed by 3405

Abstract

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and [...] Read more.

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define the conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1000 circulating swine IAV strains over the 5-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited a declining conservation with the circulating IAV strains over the same 5-year period. Conserved T cell epitope vaccines may be a useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

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15 pages, 1186 KiB

Open AccessArticle

Safety and Immunogenicity of a Novel Intranasal Influenza Vaccine (NasoVAX): A Phase 2 Randomized, Controlled Trial

by Sybil Tasker, Anna Wight O’Rourke, Anvar Suyundikov, Peta-Gay Jackson Booth, Stephan Bart, Vyjayanthi Krishnan, Jianfeng Zhang, Katie J. Anderson, Bertrand Georges and M. Scot Roberts

Vaccines 2021, 9(3), 224; https://doi.org/10.3390/vaccines9030224 - 5 Mar 2021

Cited by 14 | Viewed by 4670

Abstract

Annual influenza vaccination greatly reduces morbidity and mortality, but effectiveness remains sub-optimal. Weaknesses of current vaccines include low effectiveness against mismatched strains, lack of mucosal and other effective tissue-resident immune responses, weak cellular immune responses, and insufficiently durable immune responses. The safety and [...] Read more.

Annual influenza vaccination greatly reduces morbidity and mortality, but effectiveness remains sub-optimal. Weaknesses of current vaccines include low effectiveness against mismatched strains, lack of mucosal and other effective tissue-resident immune responses, weak cellular immune responses, and insufficiently durable immune responses. The safety and immunogenicity of NasoVAX, a monovalent intranasal influenza vaccine based on a replication-deficient adenovirus type 5 platform, were evaluated in a placebo-controlled single ascending-dose study. Sixty healthy adults (18–49 years) received a single intranasal dose of 1×10⁹ viral particles (vp), 1 × 10¹⁰ vp, or 1 × 10¹¹ vp of NasoVAX or placebo. NasoVAX was well-tolerated and elicited robust influenza-specific systemic and mucosal immune responses. The highest NasoVAX dose and the approved Fluzone^® influenza vaccine elicited comparable hemagglutination inhibition (HAI) geometric mean titers (152.8 vs. 293.4) and microneutralization (MN) geometric mean titers (142.5 vs. 162.8), with NasoVAX HAI titers maintained more than 1-year on average following a single dose. Hemagglutinin-specific T cells responses were also documented in peripheral mononuclear cell (PBMC) preparations. Consistent with the intranasal route of administration, NasoVAX elicited antigen-specific mucosal IgA responses in the nasopharyngeal cavity with an increase of approximately 2-fold over baseline GMT at the mid- and high-doses. In summary, NasoVAX appeared safe and elicited a broad immune response, including humoral, cellular, and mucosal immunity, with no impact of baseline anti-adenovirus antibody at the most immunogenic dose. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

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13 pages, 1783 KiB

Open AccessArticle

Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness

by Hirotaka Hayashi, Norikazu Isoda, Enkhbold Bazarragchaa, Naoki Nomura, Keita Matsuno, Masatoshi Okamatsu, Hiroshi Kida and Yoshihiro Sakoda

Vaccines 2020, 8(4), 768; https://doi.org/10.3390/vaccines8040768 - 16 Dec 2020

Cited by 4 | Viewed by 3515

Abstract

H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to [...] Read more.

H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

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14 pages, 265 KiB

Open AccessArticle

Immunogenicity Measures of Influenza Vaccines: A Study of 1164 Registered Clinical Trials

by Alexander Domnich, Ilaria Manini, Donatella Panatto, Giovanna Elisa Calabrò and Emanuele Montomoli

Vaccines 2020, 8(2), 325; https://doi.org/10.3390/vaccines8020325 - 19 Jun 2020

Cited by 14 | Viewed by 3533

Abstract

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe [...] Read more.

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe the patterns of use of the various immunological assays available to measure the influenza vaccine-induced adaptive immune response and to determine its correlates of protection. A total of 76.5% of the studies included in our analysis measured only the humoral immune response. Among these, the hemagglutination-inhibition assay was by far the most widely used. Other, less common, humoral immune response assays were: virus neutralization (21.7%), enzyme-linked immunosorbent (10.1%), single radial hemolysis (4.6%), and assays able to quantify anti-neuraminidase antibodies (1.7%). By contrast, cell-mediated immunity was quantified in only 23.5% of studies. Several variables were significantly associated with the use of single assays. Specifically, some influenza vaccine types (e.g., adjuvanted, live attenuated and cell culture-derived or recombinant), study phase and study sponsorship pattern were usually found to be statistically significant predictors. We discuss the principal findings and make some suggestions from the point of view of the various stakeholders. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

14 pages, 1799 KiB

Open AccessArticle

Influenza Anti-Stalk Antibodies: Development of a New Method for the Evaluation of the Immune Responses to Universal Vaccine

by Alessandro Manenti, Agnieszka Katarzyna Maciola, Claudia Maria Trombetta, Otfried Kistner, Elisa Casa, Inesa Hyseni, Ilaria Razzano, Alessandro Torelli and Emanuele Montomoli

Vaccines 2020, 8(1), 43; https://doi.org/10.3390/vaccines8010043 - 24 Jan 2020

Cited by 7 | Viewed by 4852

Abstract

Growing interest in universal influenza vaccines and novel administration routes has led to the development of alternative serological assays that are able to detect antibodies against conserved epitopes. We present a competitive ELISA method that is able to accurately determine the ratio of [...] Read more.

Growing interest in universal influenza vaccines and novel administration routes has led to the development of alternative serological assays that are able to detect antibodies against conserved epitopes. We present a competitive ELISA method that is able to accurately determine the ratio of serum immunoglobulin G directed against the different domains of the hemagglutinin, the head and the stalk. Human serum samples were treated with two variants of the hemagglutinin protein from the A/California/7/2009 influenza virus. The signals detected were assigned to different groups of antibodies and presented as a ratio between head and stalk domains. A subset of selected sera was also tested by hemagglutination inhibition, single radial hemolysis, microneutralization, and enzyme-linked lectin assays. Pre-vaccination samples from adults showed a quite high presence of anti-stalk antibodies, and the results were substantially in line with those of the classical serological assays. By contrast, pre-vaccination samples from children did not present anti-stalk antibodies, and the majority of the anti-hemagglutinin antibodies that were detected after vaccination were directed against the head domain. The presented approach, when supported by further assays, can be used to assess the presence of specific anti-stalk antibodies and the potential boost of broadly protective antibodies, especially in the case of novel universal influenza vaccine approaches. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

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