We developed a novel vaccine platform based on a paramyxoviral, genome replication-deficient Sendaivirus vector that can express heterologous genes inserted into the genome. To validate the novel approachin vivo, we generated a combined vaccine candidate against human respiratory syncytial virus (RSV)and human parainfluenza virus type 3 (PIV3). The present study compares two different methods ofdisplaying heterologous antigens: (i) the RSV fusion (F) protein, encoded as a secretable version in anadditional transcription unit, serves as an antigen only after being expressed in infected cells; (ii) PIV3fusion (F) and hemagglutinin-neuraminidase (HN) genes, replacing Sendai counterparts in the vectorgenome, are also expressed as structural components on the surface of vaccine particles. The efficacyof this prototype vaccine was assessed in a mouse model after mucosal administration. The vaccinecandidate was able to elicit specific mucosal, humoral and T cell-mediated immune responses againstRSV and PIV3. However, PIV3 antigen display on the vaccine particles’ surface induced higher antibodytiters than the RSV antigen, being expressed only after cell infection. Consequently, this construct inducedan adequate neutralizing antibody response only to PIV3. Finally, replicating virus particles were notdetected in the lungs of immunized mice, confirming the genome stability and replication deficiencyof this vaccine vector in vivo. Both factors can contribute substantially to the safety profile of vaccinecandidates. In conclusion, this replication-deficient Sendai vector represents an efficient platform thatcan be used for vaccine developments against various viral pathogens.

Wiegand, M., GORI SAVELLINI, G., Martorelli, B., Bossow, S., Neubert, W.j., Cusi, M.G. (2013). Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. VACCINE, 31(37), 3888-3893 [10.1016/j.vaccine.2013.06.053].

Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector.

GORI SAVELLINI, GIANNI;MARTORELLI, BARBARA;CUSI, MARIA GRAZIA
2013-01-01

Abstract

We developed a novel vaccine platform based on a paramyxoviral, genome replication-deficient Sendaivirus vector that can express heterologous genes inserted into the genome. To validate the novel approachin vivo, we generated a combined vaccine candidate against human respiratory syncytial virus (RSV)and human parainfluenza virus type 3 (PIV3). The present study compares two different methods ofdisplaying heterologous antigens: (i) the RSV fusion (F) protein, encoded as a secretable version in anadditional transcription unit, serves as an antigen only after being expressed in infected cells; (ii) PIV3fusion (F) and hemagglutinin-neuraminidase (HN) genes, replacing Sendai counterparts in the vectorgenome, are also expressed as structural components on the surface of vaccine particles. The efficacyof this prototype vaccine was assessed in a mouse model after mucosal administration. The vaccinecandidate was able to elicit specific mucosal, humoral and T cell-mediated immune responses againstRSV and PIV3. However, PIV3 antigen display on the vaccine particles’ surface induced higher antibodytiters than the RSV antigen, being expressed only after cell infection. Consequently, this construct inducedan adequate neutralizing antibody response only to PIV3. Finally, replicating virus particles were notdetected in the lungs of immunized mice, confirming the genome stability and replication deficiencyof this vaccine vector in vivo. Both factors can contribute substantially to the safety profile of vaccinecandidates. In conclusion, this replication-deficient Sendai vector represents an efficient platform thatcan be used for vaccine developments against various viral pathogens.
2013
Wiegand, M., GORI SAVELLINI, G., Martorelli, B., Bossow, S., Neubert, W.j., Cusi, M.G. (2013). Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. VACCINE, 31(37), 3888-3893 [10.1016/j.vaccine.2013.06.053].
File in questo prodotto:
File Dimensione Formato  
Vaccine 2013 .pdf

non disponibili

Tipologia: Pre-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.12 MB
Formato Adobe PDF
1.12 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/44558
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo