Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01
<p>Abstract</p> <p>Background</p> <p>The development of an asexual blood stage vaccine against <it>Plasmodium falciparum</it> malaria based on the major merozoite surface protein-1 (MSP1) antigen is founded on the protective efficacy observed in preclinical...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2013-01-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://www.malariajournal.com/content/12/1/29 |
| _version_ | 1818520601418006528 |
|---|---|
| author | Otsyula Nekoye Angov Evelina Bergmann-Leitner Elke Koech Margaret Khan Farhat Bennett Jason Otieno Lucas Cummings James Andagalu Ben Tosh Donna Waitumbi John Richie Nancy Shi Meng Miller Lori Otieno Walter Otieno Godfrey Allan Ware Lisa House Brent Godeaux Olivier Dubois Marie-Claude Ogutu Bernhards Ballou W Ripley Soisson Lorraine Diggs Carter Cohen Joe Polhemus Mark Heppner D Gray Ockenhouse Christian F Spring Michele D |
| author_facet | Otsyula Nekoye Angov Evelina Bergmann-Leitner Elke Koech Margaret Khan Farhat Bennett Jason Otieno Lucas Cummings James Andagalu Ben Tosh Donna Waitumbi John Richie Nancy Shi Meng Miller Lori Otieno Walter Otieno Godfrey Allan Ware Lisa House Brent Godeaux Olivier Dubois Marie-Claude Ogutu Bernhards Ballou W Ripley Soisson Lorraine Diggs Carter Cohen Joe Polhemus Mark Heppner D Gray Ockenhouse Christian F Spring Michele D |
| author_sort | Otsyula Nekoye |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The development of an asexual blood stage vaccine against <it>Plasmodium falciparum</it> malaria based on the major merozoite surface protein-1 (MSP1) antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP1<sub>42</sub> has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites.</p> <p>Methods</p> <p>Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP1<sub>42</sub> in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP1<sub>42</sub> in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator.</p> <p>Results</p> <p>In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele) previously tested at both study sites.</p> <p>Conclusions</p> <p>Given that the primary effector mechanism for blood stage vaccine targets is humoral, the antibody responses demonstrated to this vaccine candidate, both quantitative (total antibody titres) and qualitative (functional antibodies inhibiting parasite growth) warrant further consideration of its application in endemic settings.</p> <p>Trial registrations</p> <p>Clinical Trials NCT00666380</p> |
| first_indexed | 2024-12-11T01:39:39Z |
| format | Article |
| id | doaj.art-6ee036a387234e1aa41bb45efe455f9b |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-11T01:39:39Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-6ee036a387234e1aa41bb45efe455f9b2022-12-22T01:25:05ZengBMCMalaria Journal1475-28752013-01-011212910.1186/1475-2875-12-29Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01Otsyula NekoyeAngov EvelinaBergmann-Leitner ElkeKoech MargaretKhan FarhatBennett JasonOtieno LucasCummings JamesAndagalu BenTosh DonnaWaitumbi JohnRichie NancyShi MengMiller LoriOtieno WalterOtieno Godfrey AllanWare LisaHouse BrentGodeaux OlivierDubois Marie-ClaudeOgutu BernhardsBallou W RipleySoisson LorraineDiggs CarterCohen JoePolhemus MarkHeppner D GrayOckenhouse Christian FSpring Michele D<p>Abstract</p> <p>Background</p> <p>The development of an asexual blood stage vaccine against <it>Plasmodium falciparum</it> malaria based on the major merozoite surface protein-1 (MSP1) antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP1<sub>42</sub> has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites.</p> <p>Methods</p> <p>Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP1<sub>42</sub> in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP1<sub>42</sub> in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator.</p> <p>Results</p> <p>In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele) previously tested at both study sites.</p> <p>Conclusions</p> <p>Given that the primary effector mechanism for blood stage vaccine targets is humoral, the antibody responses demonstrated to this vaccine candidate, both quantitative (total antibody titres) and qualitative (functional antibodies inhibiting parasite growth) warrant further consideration of its application in endemic settings.</p> <p>Trial registrations</p> <p>Clinical Trials NCT00666380</p>http://www.malariajournal.com/content/12/1/29MalariaVaccineMerozoite surface protein-1<it>Plasmodium</it> |
| spellingShingle | Otsyula Nekoye Angov Evelina Bergmann-Leitner Elke Koech Margaret Khan Farhat Bennett Jason Otieno Lucas Cummings James Andagalu Ben Tosh Donna Waitumbi John Richie Nancy Shi Meng Miller Lori Otieno Walter Otieno Godfrey Allan Ware Lisa House Brent Godeaux Olivier Dubois Marie-Claude Ogutu Bernhards Ballou W Ripley Soisson Lorraine Diggs Carter Cohen Joe Polhemus Mark Heppner D Gray Ockenhouse Christian F Spring Michele D Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01 Malaria Journal Malaria Vaccine Merozoite surface protein-1 <it>Plasmodium</it> |
| title | Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01 |
| title_full | Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01 |
| title_fullStr | Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01 |
| title_full_unstemmed | Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01 |
| title_short | Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen <it>Plasmodium falciparum</it> FVO merozoite surface protein-1 (MSP1<sub>42</sub>) administered intramuscularly with adjuvant system AS01 |
| title_sort | results from tandem phase 1 studies evaluating the safety reactogenicity and immunogenicity of the vaccine candidate antigen it plasmodium falciparum it fvo merozoite surface protein 1 msp1 sub 42 sub administered intramuscularly with adjuvant system as01 |
| topic | Malaria Vaccine Merozoite surface protein-1 <it>Plasmodium</it> |
| url | http://www.malariajournal.com/content/12/1/29 |
| work_keys_str_mv | AT otsyulanekoye resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT angovevelina resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT bergmannleitnerelke resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT koechmargaret resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT khanfarhat resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT bennettjason resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT otienolucas resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT cummingsjames resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT andagaluben resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT toshdonna resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT waitumbijohn resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT richienancy resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT shimeng resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT millerlori resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT otienowalter resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT otienogodfreyallan resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT warelisa resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT housebrent resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT godeauxolivier resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT duboismarieclaude resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT ogutubernhards resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT ballouwripley resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT soissonlorraine resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT diggscarter resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT cohenjoe resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT polhemusmark resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT heppnerdgray resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT ockenhousechristianf resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 AT springmicheled resultsfromtandemphase1studiesevaluatingthesafetyreactogenicityandimmunogenicityofthevaccinecandidateantigenitplasmodiumfalciparumitfvomerozoitesurfaceprotein1msp1sub42subadministeredintramuscularlywithadjuvantsystemas01 |