Nonstructural Protein 2 (nsP2) of Chikungunya Virus (CHIKV) Enhances Protective Immunity Mediated by a CHIKV Envelope Protein Expressing DNA Vaccine

Abstract

Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv + pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.

Cellular and Molecular Immune Response to Chikungunya Virus Infection

“…Over the years, several vaccine candidates were evaluated as possible preventive approaches. Among those are inactivated (Rudd et al, 2015 ; DeZure et al, 2016 ) and live attenuated (Edelman et al, 2000 ; Plante et al, 2011 ; Chu et al, 2013 ; Hallengärd et al, 2014 ; Roy et al, 2014 ; Roques et al, 2017 ) viruses, DNA (Mallilankaraman et al, 2011 ; Bao et al, 2013 ; Hallengärd et al, 2014 ; Tretyakova et al, 2014 ; Muthumani et al, 2016 ; Roques et al, 2017 ) and subunit (Metz et al, 2011 , 2013 ; Khan et al, 2012 ) vaccines, as well as vaccines that are based on virus-like particles (VLPs) obtained from yeast (Saraswat et al, 2016 ), insect (Metz et al, 2013 ) and mammalian cells (Akahata et al, 2010 ; Chang et al, 2014 ). A large group of promising vaccine candidates takes advantage of chimeric avirulent backbones of measles (Brandler et al, 2013 ; Ramsauer et al, 2015 ) and vaccinia viruses (García-Arriaza et al, 2014 ; Weger-Lucarelli et al, 2014 ), adenovirus (Wang et al, 2011a ), vesiculovirus (Chattopadhyay et al, 2013 ) and alternative alphaviruses (Wang et al, 2011b ; Erasmus et al, 2017 ).…”

Vaccine and Therapeutic Options To Control Chikungunya Virus

“…Additionally, outbred mice were protected against disease upon challenge after 3 immunization doses. Further development of the system included the addition of a plasmid with the nsP2 sequence, which was found to enhance the effect of the envelope protein vaccine (75).…”

New Approaches to Chikungunya Virus Vaccine Development

“…This vaccine also proved to be immunogenic in rhesus macaques, eliciting cellular and humoral responses; they were not challenged with the virus to assess protection, but their response to the vaccine was similar to that of convalescent humans [36]. Later, in 2013, Bao and collaborators [37] added the nonstructural protein-2 (nsP2) as adjuvant to envelope (E2) DNA vaccine. This formulation significantly increases both cellular and humoral immune responses in particular specific NAbs and protection of mice against viral challenge [37].…”

“…Later, in 2013, Bao and collaborators [37] added the nonstructural protein-2 (nsP2) as adjuvant to envelope (E2) DNA vaccine. This formulation significantly increases both cellular and humoral immune responses in particular specific NAbs and protection of mice against viral challenge [37].…”

“…A bright future may be closer than expected. [35] DNA vaccine: envelope proteins (E1+E2+E3) 2011 Pre-clinical (Mice/Macaques) [36] DNA vaccine: envelope protein + nonstructural gene 2 (nsP2) as an adjuvant 2013 Pre-clinical (Mice) [37] DNA vaccine: encoded the full-length infectious RNA genome of live attenuated vaccine 181/25…”