VLPs generated by the fusion of RSV-F or hMPV-F glycoprotein to HIV-Gag show improved immunogenicity and neutralizing response in mice.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julia Blanco reports financial support and equipment, drugs, or supplies were provided by Merck Sharp & Dohme Corp. Anna Pons-Grifols reports financial support was provided by Government of Catalonia Agency for Administration of University and Research Grants and European Social Fund. Julia Blanco reports a relationship with AlbaJuna Therapeutics SL that includes: board membership, employment, and equity or stocks. Jorge Carillo reports a relationship with AlbaJuna Therapeutics SL that includes: board membership, employment, and equity or stocks. Bonaventura Clotet reports a relationship with AlbaJuna Therapeutics SL that includes: board membership, employment, and equity or stocks. Eberhard Durr reports a relationship with Merck Sharp & Dohme Corp that includes: employment. Gregory O’Donnell reports a relationship with Merck Sharp & Dohme Corp that includes: employment. Silveria Rodriguez reports a relationship with Merck Sharp & Dohme Corp that includes: employment. Joel Mane reports a relationship with Merck Sharp & Dohme Corp that includes: employment. Lan Zhang reports a relationship with Merck Sharp & Dohme Corp that includes: employment. Eberhard Durr reports a relationship with Merck & Co Inc that includes: equity or stocks. Gregory O’Donnell reports a relationship with Merck & Co Inc that includes: equity or stocks. Silveria Rodriguez reports a relationship with Merck & Co Inc that includes: equity or stocks. Joel Mane reports a relationship with Merck & Co Inc that includes: equity or stocks. Lan Zhang reports a relationship with Merck & Co Inc that includes: equity or stocks. Bonaventura Clotet has patent #EP1638234.4 “Virus-like particles with high density coating for the production of neutralizing antibodies” licensed to Irsicaixa. Jorge Carrillo has patent #EP1638234.4 “Virus-like particles with high density coating for the production of neutralizing antibodies” licensed to Irsicaixa. Julia Blanco has patent #EP1638234.4 “Virus-like particles with high density coating for the production of neutralizing antibodies” licensed to Irsicaixa. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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