IgG subclass switch in volunteers repeatedly immunized with the full-length plasmodium falciparum Merozoite Surface Protein 1 (MSP1)
Vaccines are highly effective tools against infectious diseases and are also considered necessary in the fight against malaria. Vaccine-induced immunity is frequently mediated by antibodies. We have recently conducted a first-in-human clinical trial featuring SumayaVac-1, a malaria vaccine based on...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
17 February 2024
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| In: |
Vaccines
Year: 2024, Volume: 12, Issue: 2, Pages: 1-19 |
| ISSN: | 2076-393X |
| DOI: | 10.3390/vaccines12020208 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/vaccines12020208 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2076-393X/12/2/208 
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| Author Notes: | Veronika Rathay, Kristin Fürle, Viktoria Kiehl, Anne Ulmer, Michael Lanzer and Richard Thomson-Luque |
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| 245 | 1 | 0 | |a IgG subclass switch in volunteers repeatedly immunized with the full-length plasmodium falciparum Merozoite Surface Protein 1 (MSP1) |c Veronika Rathay, Kristin Fürle, Viktoria Kiehl, Anne Ulmer, Michael Lanzer and Richard Thomson-Luque |
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| 520 | |a Vaccines are highly effective tools against infectious diseases and are also considered necessary in the fight against malaria. Vaccine-induced immunity is frequently mediated by antibodies. We have recently conducted a first-in-human clinical trial featuring SumayaVac-1, a malaria vaccine based on the recombinant, full-length merozoite surface protein 1 (MSP1FL) formulated with GLA-SE as an adjuvant. Vaccination with MSP1FL was safe and elicited sustainable IgG antibody titers that exceeded those observed in semi-immune populations from Africa. Moreover, IgG antibodies stimulated various Fc-mediated effector mechanisms associated with protection against malaria. However, these functionalities gradually waned. Here, we show that the initial two doses of SumayaVac-1 primarily induced the cytophilic subclasses IgG1 and IgG3. Unexpectedly, a shift in the IgG subclass composition occurred following the third and fourth vaccinations. Specifically, there was a progressive transition to IgG4 antibodies, which displayed a reduced capacity to engage in Fc-mediated effector functions and also exhibited increased avidity. In summary, our analysis of antibody responses to MSP1FL vaccination unveils a temporal shift towards noninflammatory IgG4 antibodies. These findings underscore the importance of considering the impact of IgG subclass composition on vaccine-induced immunity, particularly concerning Fc-mediated effector functions. This knowledge is pivotal in guiding the design of optimal vaccination strategies against malaria, informing decision making for future endeavors in this critical field. | ||
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