Recent Approaches in Hantavirus Vaccine Development

Piet Maes; Jan Clement; Marc Van Ranst

Disclosures

Expert Rev Vaccines. 2009;8(1):67-76. 

In This Article

Genetic Vaccines

Nucleic acid vaccines or DNA vaccines, usually based on plasmid DNA or linear DNA, have been demonstrated as a promising vaccination strategy for various viral infections. Numerous studies have shown that injection of naked DNA stimulates effective and long-lived immune responses to the protein antigens encoded by the gene vaccine.[91] DNA-based vaccination not only provides a strategy for a relatively safe modality capable of inducing both cytotoxic T cells and antibodies, but also offers an easy mehtod of generating multivalent vaccines. Several groups have utilized the whole or fragmented nucleocapsid protein, and the membrane glycoproteins Gn and Gc of Andes virus, Hantaan virus, Puumala virus, Seoul virus and Sin Nombre virus as immunogens.[35,92,93,94,95,96,97,98,99,100,101,102,103] These plasmids have been shown to offer protection against experimental infection in hamster, mouse or macaque models. Both the nucleocapsid protein and the membrane Gn and Gc glycoproteins elicited strong specific antibody responses. Moreover, constructs expressing the membrane Gn and Gc glycoproteins exhibited the desired neutralizing antibody responses. Constructs expressing the full-length nucleocapsid proteins of Puumala virus, Seoul virus and Sin Nombre virus were found to be crossreactive.[104] Highly crossneutralizing antibodies to other HPS-associated hantaviruses, including Sin Nombre virus, were also described after vaccination of rhesus macaques with an Andes virus M segment DNA vaccine.[94] In passive transfer experiments where antibodies raised in rabbits were used in an M segment-based DNA vaccine, Syrian hamsters were completely protected against intranasal challenge with Andes virus.[100] In yet another study, the inclusion of immunomodulatory proteins, such as the heat-shock protein 70[105] or IL-12[106] next to full-length Hantaan virus S segment DNA, increased both humoral and cellular immune responses in C57Bl/6 mice.

Alphavirus (Sindbis virus) replicons have also been evaluated as a possible DNA-based vaccine approach. In alphavirus replicons, the structural protein genes are replaced by a foreign gene, such as an immunogen. These replicons can be packaged into extracellular particles by cotransfection of cells with both replicons and defective helper RNA. The latter are not selfreplicating but will be replicated and transcribe the alphavirus subgenomic RNA coding for the viral structural proteins if the required nonstructural proteins are expressed from the replicons.[107] Packaged alphavirus replicons provide a method of delivering foreign genes of interest into host cells without using replication-competent virus as a vector.[107,108] Packaged Sindbis virus replicons expressing the Seoul virus nucleocapsid protein or the membrane glycoproteins Gn and Gc were used to immunize Syrian hamsters.[97] The hamsters developed a nucleocapsid-specific antibody response but were found not to be protected from virus challenge. This contrasts with other studies where exogenously expressed recombinant Seoul virus nucleocapsid proteins protected mice from challenge (see previous section). Only some of the hamsters immunized with replicons carrying the Gn/Gc membrane glycoproteins developed neutralizing antibodies and were protected from challenge with Seoul virus.[97]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....