Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

Kelly E Seaton; Rachel L Spreng; Milite Abraha; Matthew Reichartz; Michelle Rojas; Frederick Feely 2nd; Richard H C Huntwork; Sheetij Dutta; Sarah V Mudrak; S Munir Alam; Scott Gregory; Erik Jongert; Margherita Coccia; Fernando Ulloa-Montoya; Ulrike Wille-Reece; Georgia D Tomaras; S Moses Dennison

doi:10.1038/s41541-021-00372-x

Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

NPJ Vaccines. 2021 Aug 30;6(1):110. doi: 10.1038/s41541-021-00372-x.

Authors

Kelly E Seaton^#^{1

2

3}, Rachel L Spreng^#^{4

5}, Milite Abraha^{6

7

8}, Matthew Reichartz^{6

7

8}, Michelle Rojas⁶, Frederick Feely 2nd^{6

7

8}, Richard H C Huntwork^{6

7

8}, Sheetij Dutta⁹, Sarah V Mudrak^{6

7

8}, S Munir Alam^{6

10}, Scott Gregory¹¹, Erik Jongert¹², Margherita Coccia¹², Fernando Ulloa-Montoya¹², Ulrike Wille-Reece^{11

13}, Georgia D Tomaras^#^{14

15

16

17

18}, S Moses Dennison^#^{19

20

21}

Affiliations

¹ Duke Human Vaccine Institute, Durham, NC, USA. [email protected].
² Duke Center for Human Systems Immunology, Durham, NC, USA. [email protected].
³ Duke University Department of Surgery, Durham, NC, USA. [email protected].
⁴ Duke Human Vaccine Institute, Durham, NC, USA. [email protected].
⁵ Duke Center for Human Systems Immunology, Durham, NC, USA. [email protected].
⁶ Duke Human Vaccine Institute, Durham, NC, USA.
⁷ Duke Center for Human Systems Immunology, Durham, NC, USA.
⁸ Duke University Department of Surgery, Durham, NC, USA.
⁹ Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹⁰ Duke University Department of Pathology, Durham, NC, USA.
¹¹ PATH's Malaria Vaccine Initiative, Washington, DC, USA.
¹² GSK, Rixensart, Belgium.
¹³ GSK, Rockville, MD, USA.
¹⁴ Duke Human Vaccine Institute, Durham, NC, USA. [email protected].
¹⁵ Duke Center for Human Systems Immunology, Durham, NC, USA. [email protected].
¹⁶ Duke University Department of Surgery, Durham, NC, USA. [email protected].
¹⁷ Duke University Department of Immunology, Durham, NC, USA. [email protected].
¹⁸ Duke University Department of Molecular Genetics and Microbiology, Durham, NC, USA. [email protected].
¹⁹ Duke Human Vaccine Institute, Durham, NC, USA. [email protected].
²⁰ Duke Center for Human Systems Immunology, Durham, NC, USA. [email protected].
²¹ Duke University Department of Surgery, Durham, NC, USA. [email protected].

^# Contributed equally.

Abstract

RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens. Central repeat (NANP6) IgG1 magnitude correlated best with protection status in univariate analyses and was the most predictive for protection in a multivariate model. NANP6 IgG3 magnitude, CSP IgG1 magnitude, and total serum antibody dissociation phase area-under-the-curve for NANP6, CSP, NPNA3, and N-interface binding were also associated with protection status in the regimen adjusted univariate analysis. Identification of multiple immune response features that associate with protection status, such as antibody subclasses, fine specificity and avidity reported here may accelerate development of highly efficacious vaccines against P. falciparum.

Abstract

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