Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose
Chikungunya virus (CHIKV) is the causative pathogen of chikungunya fever, a mosquito-borne viral disease causing highly debilitating arthralgia that can persist for months and progress to chronic arthritis. Our previous studies have identified the CHIKV live-attenuated vaccine candidate CHIKV-NoLS....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00304/full |
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| author | Eranga Abeyratne Eranga Abeyratne Kothila Tharmarajah Kothila Tharmarajah Joseph R. Freitas Joseph R. Freitas Helen Mostafavi Helen Mostafavi Suresh Mahalingam Suresh Mahalingam Ali Zaid Ali Zaid Mehfuz Zaman Adam Taylor Adam Taylor |
| author_facet | Eranga Abeyratne Eranga Abeyratne Kothila Tharmarajah Kothila Tharmarajah Joseph R. Freitas Joseph R. Freitas Helen Mostafavi Helen Mostafavi Suresh Mahalingam Suresh Mahalingam Ali Zaid Ali Zaid Mehfuz Zaman Adam Taylor Adam Taylor |
| author_sort | Eranga Abeyratne |
| collection | DOAJ |
| description | Chikungunya virus (CHIKV) is the causative pathogen of chikungunya fever, a mosquito-borne viral disease causing highly debilitating arthralgia that can persist for months and progress to chronic arthritis. Our previous studies have identified the CHIKV live-attenuated vaccine candidate CHIKV-NoLS. Like most live-attenuated vaccines, attenuated replication of CHIKV-NoLS has the potential to limit scalable production. To overcome production limits, as well as other drawbacks of live-attenuated vaccines, we developed an in vivo liposome RNA delivery system to deliver the self-replicating RNA genome of CHIKV-NoLS directly into mice, allowing the recipients' body to produce the live-attenuated vaccine particles. CAF01 liposomes were able to deliver replication-competent CHIKV-NoLS RNA in vitro. Immunodeficient AG129 mice inoculated with liposome-delivered CHIKV-NoLS RNA developed viremia and disease signs representative of this lethal model of CHIKV infection, demonstrating de novo vaccine particle production in vivo. In immunocompetent C57BL/6 mice, liposome-delivered CHIKV-NoLS RNA inoculation was associated with reduced IgM and IgG levels with low antibody CHIKV-neutralizing capacity, compared to vaccination with the original live-attenuated vaccine CHIKV-NoLS. One dose of liposome-delivered CHIKV-NoLS RNA did not provide systemic protection from CHIKV wild-type (WT) challenge but was found to promote an early onset of severe CHIKV-induced footpad swelling. Liposome-delivered CHIKV-NoLS RNA inoculation did, however, provide local protection from CHIKV-WT challenge in the ipsilateral foot after one dose. Results suggest that in the presence of low CHIKV-specific neutralizing antibody levels, local inflammatory responses, likely brought on by liposome adjuvants, have a role in the protection of CHIKV-induced footpad swelling in the ipsilateral foot of mice inoculated with liposome-delivered CHIKV-NoLS RNA. Low IgG and CHIKV-specific neutralizing antibody levels may be responsible for early onset of severe swelling in the feet of CHIKV-WT-challenged mice. These results support previous studies that suggest CHIKV is vulnerable to antibody-mediated enhancement of disease. Further studies using booster regimes aim to demonstrate the potential for liposomes to deliver the self-replicating RNA genome of live-attenuated vaccines and offer a novel immunization strategy. |
| first_indexed | 2024-12-24T05:18:46Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T05:18:46Z |
| publishDate | 2020-03-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-5eaa0a03bcb24eb194585b0ea07e8bed2022-12-21T17:13:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-03-011110.3389/fimmu.2020.00304496735Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One DoseEranga Abeyratne0Eranga Abeyratne1Kothila Tharmarajah2Kothila Tharmarajah3Joseph R. Freitas4Joseph R. Freitas5Helen Mostafavi6Helen Mostafavi7Suresh Mahalingam8Suresh Mahalingam9Ali Zaid10Ali Zaid11Mehfuz Zaman12Adam Taylor13Adam Taylor14The Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Southport, QLD, AustraliaChikungunya virus (CHIKV) is the causative pathogen of chikungunya fever, a mosquito-borne viral disease causing highly debilitating arthralgia that can persist for months and progress to chronic arthritis. Our previous studies have identified the CHIKV live-attenuated vaccine candidate CHIKV-NoLS. Like most live-attenuated vaccines, attenuated replication of CHIKV-NoLS has the potential to limit scalable production. To overcome production limits, as well as other drawbacks of live-attenuated vaccines, we developed an in vivo liposome RNA delivery system to deliver the self-replicating RNA genome of CHIKV-NoLS directly into mice, allowing the recipients' body to produce the live-attenuated vaccine particles. CAF01 liposomes were able to deliver replication-competent CHIKV-NoLS RNA in vitro. Immunodeficient AG129 mice inoculated with liposome-delivered CHIKV-NoLS RNA developed viremia and disease signs representative of this lethal model of CHIKV infection, demonstrating de novo vaccine particle production in vivo. In immunocompetent C57BL/6 mice, liposome-delivered CHIKV-NoLS RNA inoculation was associated with reduced IgM and IgG levels with low antibody CHIKV-neutralizing capacity, compared to vaccination with the original live-attenuated vaccine CHIKV-NoLS. One dose of liposome-delivered CHIKV-NoLS RNA did not provide systemic protection from CHIKV wild-type (WT) challenge but was found to promote an early onset of severe CHIKV-induced footpad swelling. Liposome-delivered CHIKV-NoLS RNA inoculation did, however, provide local protection from CHIKV-WT challenge in the ipsilateral foot after one dose. Results suggest that in the presence of low CHIKV-specific neutralizing antibody levels, local inflammatory responses, likely brought on by liposome adjuvants, have a role in the protection of CHIKV-induced footpad swelling in the ipsilateral foot of mice inoculated with liposome-delivered CHIKV-NoLS RNA. Low IgG and CHIKV-specific neutralizing antibody levels may be responsible for early onset of severe swelling in the feet of CHIKV-WT-challenged mice. These results support previous studies that suggest CHIKV is vulnerable to antibody-mediated enhancement of disease. Further studies using booster regimes aim to demonstrate the potential for liposomes to deliver the self-replicating RNA genome of live-attenuated vaccines and offer a novel immunization strategy.https://www.frontiersin.org/article/10.3389/fimmu.2020.00304/fullchikungunyavaccineliposomeRNAlive-attenuated |
| spellingShingle | Eranga Abeyratne Eranga Abeyratne Kothila Tharmarajah Kothila Tharmarajah Joseph R. Freitas Joseph R. Freitas Helen Mostafavi Helen Mostafavi Suresh Mahalingam Suresh Mahalingam Ali Zaid Ali Zaid Mehfuz Zaman Adam Taylor Adam Taylor Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose Frontiers in Immunology chikungunya vaccine liposome RNA live-attenuated |
| title | Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose |
| title_full | Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose |
| title_fullStr | Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose |
| title_full_unstemmed | Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose |
| title_short | Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose |
| title_sort | liposomal delivery of the rna genome of a live attenuated chikungunya virus vaccine candidate provides local but not systemic protection after one dose |
| topic | chikungunya vaccine liposome RNA live-attenuated |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00304/full |
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