Engineering of Live Chimeric Vaccines against Human Metapneumovirus

Ogonczyk-Makowska, Daniela; Hamelin, Marie‐Ève; Boivin, Guy

doi:10.3390/pathogens9020135

Cited by 7 publications

(14 citation statements)

References 208 publications

(189 reference statements)

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“…Several live attenuated vaccines against HMPV are currently under development [ 14 , 20 , 68 ]. NIAID scientists have developed two attenuated recombinant MPV viruses, on the backbone of a human MPV strain, in which the phosphoprotein (rHMPV-Pa) or nucleoprotein (rHMPV-Na) genes are substituted by the same genes from the avian MPV subtype C [ 69 ].…”

Section: Overview Of Current Approaches To the Development Of Hmpvmentioning

confidence: 99%

“…The key issue is to select the delivery system that will provide optimal stimulation of the immune response. Currently, several viral-vectored vaccines against HMPV infection are under development (reviewed in [ 20 ]). The majority of viral-vectored vaccines use HMPV’s fusion protein as a target antigen because of its ability to induce robust HMPV-neutralizing antibodies and confer cell-mediated immunity.…”

Section: Overview Of Current Approaches To the Development Of Hmpvmentioning

confidence: 99%

“…The majority of viral-vectored vaccines use HMPV’s fusion protein as a target antigen because of its ability to induce robust HMPV-neutralizing antibodies and confer cell-mediated immunity. To date, such respiratory viruses as recombinant bovine/human PIV3 (bovine PIV backbone genes and human PIV3 F and HN surface proteins), human PIV1, and Sendai virus (a murine PIV1 virus) have been explored as potential vector systems expressing HMPV’s F protein, yielding promising results in animal models [ 20 ].…”

Section: Overview Of Current Approaches To the Development Of Hmpvmentioning

confidence: 99%

“…More advanced strategies for generating recombinant live attenuated HMPV vaccines have been explored in recent years, yielding promising results in animal models [ 7 , 20 , 21 ]. The most advanced recombinant live attenuated HMPV vaccine was tested in a phase I clinical trial in adults and children.…”

Section: Introductionmentioning

confidence: 99%

“…The results showed that the vaccine was overattenuated in HMPV-seronegative children, which led to the trial’s termination [ 22 ]. A number of recombinant protein or virus-like particle (VLP)-based HMPV vaccine candidates have also been evaluated in pre-clinical studies [ 7 , 20 ]. Most of the protein-based vaccines expressed the full-length fusion protein (F), which is the major antigenic determinant of the virus.…”

Section: Introductionmentioning

confidence: 99%

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Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus

2020

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Human metapneumovirus (HMPV) is a major cause of respiratory illnesses in children, the elderly and immunocompromised patients. Although this pathogen was only discovered in 2001, an enormous amount of research has been conducted in order to develop safe and effective vaccines to prevent people from contracting the disease. In this review, we summarize current knowledge about the most promising experimental B- and T-cell epitopes of human metapneumovirus for the rational design of HMPV vaccines using vector delivery systems, paying special attention to the conservation of these epitopes among different lineages/genotypes of HMPV. The prospects of the successful development of an epitope-based HMPV vaccine are discussed in the context of recent findings regarding HMPV’s ability to modulate host immunity. In particular, we discuss the lack of data on experimental human CD4 T-cell epitopes for HMPV despite the role of CD4 lymphocytes in both the induction of higher neutralizing antibody titers and the establishment of CD8 memory T-cell responses. We conclude that current research should be focused on searching for human CD4 T-cell epitopes of HMPV that can help us to design a safe and cross-protective epitope-based HMPV vaccine.

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Section: Overview Of Current Approaches To the Development Of Hmpvmentioning

confidence: 99%

Section: Overview Of Current Approaches To the Development Of Hmpvmentioning

confidence: 99%

Section: Overview Of Current Approaches To the Development Of Hmpvmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus

2020

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Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice

Ogonczyk-Makowska,

Brun,

Vacher

et al. 2024

npj Vaccines

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Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.

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Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus

Ma,

Zhu,

et al. 2024

Human Vaccines & Immunotherapeutics

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Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants β-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine’s efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.

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Engineering of Live Chimeric Vaccines against Human Metapneumovirus

Cited by 7 publications

References 208 publications

Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus

Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus

Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice

Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus

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