Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin
Abstract Background Indian-origin rhesus (InR) are preferred for research, but strict export restrictions continue to limit their use. Chinese-origin rhesus (ChR), although easier to procure, are genetically distinct from InR and differ in their immune response to infectious agents, such as the Simi...
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12936-019-3014-5 |
| _version_ | 1818363215495561216 |
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| author | Monica L. Martin Alexis A. Bitzer Andrew Schrader Elke S. Bergmann-Leitner Kim Soto Xiaoyan Zou Zoltan Beck Gary R. Matyas Sheetij Dutta |
| author_facet | Monica L. Martin Alexis A. Bitzer Andrew Schrader Elke S. Bergmann-Leitner Kim Soto Xiaoyan Zou Zoltan Beck Gary R. Matyas Sheetij Dutta |
| author_sort | Monica L. Martin |
| collection | DOAJ |
| description | Abstract Background Indian-origin rhesus (InR) are preferred for research, but strict export restrictions continue to limit their use. Chinese-origin rhesus (ChR), although easier to procure, are genetically distinct from InR and differ in their immune response to infectious agents, such as the Simian Immunodeficiency Virus. The most advanced malaria vaccine, RTS,S (GlaxoSmithKline), is based on the circumsporozoite protein (CSP) of Plasmodium falciparum. The efficacy of RTS,S vaccine in the field remains low and short-lived; efforts are underway to improve CSP-based vaccines. Rhesus models can accelerate preclinical down-selection of the next generation of malaria vaccines. This study was used to determine if the safety and immunogenicity outcomes following vaccination with a CSP vaccine would differ in the InR and ChR models, given the genetic differences between the two sub-populations of rhesus. Methods The FMP013 vaccine, was composed of nearly full-length soluble P. falciparum CSP produced in Escherichia coli and was adjuvanted with the Army liposomal formulation (ALFQ). Three doses of the vaccine were administered in InR and ChR (n = 6) at 1-month intervals and the antibody and T cell responses were assessed. Results Local and systemic toxicity profile of FMP013 vaccine in InR and ChR were similar and they revealed that the FMP013 vaccine was safe and caused only mild and transient inflammatory adverse reactions. Following the first 2 vaccines, there was a slower acquisition of antibodies to the CSP repeat region in ChR. However after the 3rd vaccination the titers in the two models were comparable. The ChR group repeat-specific antibodies had higher avidity and ChR group showed higher inhibition of liver stage development activity compared to InR. There was no difference in T-cell responses to the FMP013 vaccine between the two models. Conclusions A difference in the quality of serological responses was detected between the two sub-populations of rhesus. However, both models confirmed that FMP013/ALFQ vaccine was safe, highly immunogenic, elicited functional antibodies and T-cell responses. Overall, the data suggests that rhesus of Indian and Chinese origins can be interchangeably used to compare the safety and immunogenicity of next-generation of malaria vaccines and adjuvants. |
| first_indexed | 2024-12-13T21:44:56Z |
| format | Article |
| id | doaj.art-23ea6cd643c5430d9fa8a3cb1db024e3 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-13T21:44:56Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-23ea6cd643c5430d9fa8a3cb1db024e32022-12-21T23:30:26ZengBMCMalaria Journal1475-28752019-11-0118111010.1186/s12936-019-3014-5Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese originMonica L. Martin0Alexis A. Bitzer1Andrew Schrader2Elke S. Bergmann-Leitner3Kim Soto4Xiaoyan Zou5Zoltan Beck6Gary R. Matyas7Sheetij Dutta8Division of Veterinary Medicine, Walter Reed Army Institute of ResearchStructural Biologics Laboratory, Malaria Biologics Branch, Walter Reed Army Institute of ResearchDivision of Veterinary Medicine, Walter Reed Army Institute of ResearchImmunology Core, Malaria Biologics Branch, Walter Reed Army Institute of ResearchStructural Biologics Laboratory, Malaria Biologics Branch, Walter Reed Army Institute of ResearchMalaria Department, Naval Medical Research CenterMilitary HIV Research Program, Walter Reed Army Institute of ResearchMilitary HIV Research Program, Walter Reed Army Institute of ResearchStructural Biologics Laboratory, Malaria Biologics Branch, Walter Reed Army Institute of ResearchAbstract Background Indian-origin rhesus (InR) are preferred for research, but strict export restrictions continue to limit their use. Chinese-origin rhesus (ChR), although easier to procure, are genetically distinct from InR and differ in their immune response to infectious agents, such as the Simian Immunodeficiency Virus. The most advanced malaria vaccine, RTS,S (GlaxoSmithKline), is based on the circumsporozoite protein (CSP) of Plasmodium falciparum. The efficacy of RTS,S vaccine in the field remains low and short-lived; efforts are underway to improve CSP-based vaccines. Rhesus models can accelerate preclinical down-selection of the next generation of malaria vaccines. This study was used to determine if the safety and immunogenicity outcomes following vaccination with a CSP vaccine would differ in the InR and ChR models, given the genetic differences between the two sub-populations of rhesus. Methods The FMP013 vaccine, was composed of nearly full-length soluble P. falciparum CSP produced in Escherichia coli and was adjuvanted with the Army liposomal formulation (ALFQ). Three doses of the vaccine were administered in InR and ChR (n = 6) at 1-month intervals and the antibody and T cell responses were assessed. Results Local and systemic toxicity profile of FMP013 vaccine in InR and ChR were similar and they revealed that the FMP013 vaccine was safe and caused only mild and transient inflammatory adverse reactions. Following the first 2 vaccines, there was a slower acquisition of antibodies to the CSP repeat region in ChR. However after the 3rd vaccination the titers in the two models were comparable. The ChR group repeat-specific antibodies had higher avidity and ChR group showed higher inhibition of liver stage development activity compared to InR. There was no difference in T-cell responses to the FMP013 vaccine between the two models. Conclusions A difference in the quality of serological responses was detected between the two sub-populations of rhesus. However, both models confirmed that FMP013/ALFQ vaccine was safe, highly immunogenic, elicited functional antibodies and T-cell responses. Overall, the data suggests that rhesus of Indian and Chinese origins can be interchangeably used to compare the safety and immunogenicity of next-generation of malaria vaccines and adjuvants.http://link.springer.com/article/10.1186/s12936-019-3014-5Circumsporozoite proteinCSPRhesusChinese originIndian originMacaque |
| spellingShingle | Monica L. Martin Alexis A. Bitzer Andrew Schrader Elke S. Bergmann-Leitner Kim Soto Xiaoyan Zou Zoltan Beck Gary R. Matyas Sheetij Dutta Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin Malaria Journal Circumsporozoite protein CSP Rhesus Chinese origin Indian origin Macaque |
| title | Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin |
| title_full | Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin |
| title_fullStr | Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin |
| title_full_unstemmed | Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin |
| title_short | Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin |
| title_sort | comparison of immunogenicity and safety outcomes of a malaria vaccine fmp013 alfq in rhesus macaques macaca mulatta of indian and chinese origin |
| topic | Circumsporozoite protein CSP Rhesus Chinese origin Indian origin Macaque |
| url | http://link.springer.com/article/10.1186/s12936-019-3014-5 |
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