Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults

Pleguezuelos, Olga; Dille, Joep; Groen, Sofie de; Oftung, Fredrik; Niesters, Hubert G. M.; Islam, Atiqul; Næss, Lisbeth Meyer; Hungnes, Olav; Aldarij, Nuhoda; Idema, Demy L; Pérez, Ana Fernández; James, Emma L.; Frijlink, Henderik W.; Stoloff, Gregory; Groeneveld, P. H. P.; Hak, Eelko

doi:10.7326/m19-0735

Cited by 30 publications

(15 citation statements)

References 23 publications

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“…It has been proposed that vaccination with conserved epitopes of influenza virus can result in broad protection. Universal vaccination has now been developed and is undergoing clinical trials [ 56 , 57 ]. Therefore, our strategy is valuable before the availability of an effective and safe universal influenza vaccine.…”

Section: Discussionmentioning

confidence: 99%

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine

Fong

Zhang

et al. 2020

Vaccines

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We previously reported that topical imiquimod can improve the immunogenicity of the influenza vaccine. This study investigated another FDA-approved drug, miltefosine (MTF), as a vaccine adjuvant. Mice immunized with an influenza vaccine with or without MTF adjuvant were challenged by a lethal dose of influenza virus 3 or 7 days after vaccination. Survival, body weight, antibody response, histopathological changes, viral loads, cytokine levels, and T cell frequencies were compared. The MTF-adjuvanted vaccine (MTF-VAC) group had a significantly better survival rate than the vaccine-only (VAC) group, when administered 3 days (80% vs. 26.7%, p = 0.0063) or 7 days (96% vs. 65%, p = 0.0041) before influenza virus challenge. Lung damage was significantly ameliorated in the MTF-VAC group. Antibody response was significantly augmented in the MTF-VAC group against both homologous and heterologous influenza strains. There was a greater T follicular helper cell (TFH) response and an enhanced germinal center (GC) reaction in the MTF-VAC group. MTF-VAC also induced both TH1 and TH2 antigen-specific cytokine responses. MTF improved the efficacy of the influenza vaccine against homologous and heterologous viruses by improving the TFH and antibody responses. Miltefosine may also be used for other vaccines, including the upcoming vaccines for COVID-19.

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Section: Discussionmentioning

confidence: 99%

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine

Fong

Zhang

et al. 2020

Vaccines

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“…Flu-v consists of conserved peptides derived from M1, M2, and NP formulated with Montanide ISA-51 as an adjuvant. The vaccine induces cellular immunity in humans, and could reduce symptoms and viral shedding in a small human challenge study [150,151]. A recently published phase IIb study showed only a limited capacity of the vaccine to protect against mild to moderate influenza disease in experimental infections.…”

Section: Clinical Studies Of T Cell-inducing Flu Vaccinesmentioning

confidence: 99%

T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine

Schmidt

Lapuente

2021

Viruses

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Current flu vaccines rely on the induction of strain-specific neutralizing antibodies, which leaves the population vulnerable to drifted seasonal or newly emerged pandemic strains. Therefore, universal flu vaccine approaches that induce broad immunity against conserved parts of influenza have top priority in research. Cross-reactive T cell responses, especially tissue-resident memory T cells in the respiratory tract, provide efficient heterologous immunity, and must therefore be a key component of universal flu vaccines. Here, we review recent findings about T cell-based flu immunity, with an emphasis on tissue-resident memory T cells in the respiratory tract of humans and different animal models. Furthermore, we provide an update on preclinical and clinical studies evaluating T cell-evoking flu vaccines, and discuss the implementation of T cell immunity in real-life vaccine policies.

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“…In turn, FLU-v, developed by PepTcell (SEEK), is a peptide vaccine comprised of four synthetic peptides with conserved epitopes from influenza A and B strains designed to provide a broadly protective cellular immune response against influenza A and B. Results from phase IIb clinical trials showed that adjuvanted FLU-v recipients ( n = 40) were significantly less likely to develop mild to moderate influenza disease (MMID) following intranasal challenge of A/CA04/H1N1 vs. placebo ( n = 42) (32.5 vs. 54.8% p = 0.035) [ 69 , 70 , 71 ]. Nevertheless, overall the vaccine protection effect was poor.…”

Section: Novel Universal Influenza Vaccinesmentioning

confidence: 99%

Progress in the Development of Universal Influenza Vaccines

Sun

Luo

Chen

et al. 2020

Viruses

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Influenza viruses pose a significant threat to human health. They are responsible for a large number of deaths annually and have a serious impact on the global economy. There are numerous influenza virus subtypes, antigenic variations occur continuously, and epidemic trends are difficult to predict—all of which lead to poor outcomes of routine vaccination against targeted strain subtypes. Therefore, the development of universal influenza vaccines still constitutes the ideal strategy for controlling influenza. This article reviews the progress in development of universal vaccines directed against the conserved regions of hemagglutinin (HA), neuraminidase (NA), and other structural proteins of influenza viruses using new technologies and strategies with the goals of enhancing our understanding of universal influenza vaccines and providing a reference for research into the exploitation of natural immunity against influenza viruses.

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Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults

Abstract: InterventionsFLU-v is a sterile 500-μg equimolar mix of 4 lyophilized synthetic peptides (5) (Appendix Table 1, available at Annals.org). Montanide ISA-51 (mineral oil/ mannide monooleate) (SEPPIC) was used as an adjuvant to enhance immune responses to FLU-v antigens.

Cited by 30 publications

References 23 publications

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine

T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine

Progress in the Development of Universal Influenza Vaccines

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