An exploratory analysis of the entire dataset.

A, B C, D and E show the score plots of PCA model colored according to time of the sampling, type of vaccine used, area of residence (location = rural or semi-urban), gender (male and female) and anthelmintic pre-treatment (yes or no) respectively. PCA model built for the two first component cover 17% of the variance and 10 components was required to cover 50% of the variance. (TIF)</p

Exploratory analysis of the urine samples of volunteers at baseline.

A, B and C show the score plots of PCA model according to sex (male and female), anthelmintic pre-treatment (yes or no) and area of residence (location = rural or semi-urban) respectively. PCA model built for the two first component cover 26% of the variance and 6 components were required to cover 50% of the variance. D- is a cross-validated score plot of 2 class PLS-DA model with location as class identity. Model metrics: R2X = 0.232, R2Y = 0.81, Q2 = 0.40.</p

An exploratory analysis of metabolic response to vaccination on the first (A, B) and the third (C, D) vaccination rounds.

The score plots of the PCA models are colored according to time of the sampling (A, C) type of vaccine used (B, D). 17% of the variance is covered by the first 2 components and 8 components are needed to explain 50% of the variance. (TIF)</p

Metabolites that changed at day 1 post vaccination.

A, B, C, D and E show plots of metabolites that changed significantly at day 1 post vaccination. Y axis corresponds to metabolite log transformed concentration and X axis to timepoint. Dot and line are colored according to vaccine type (control = Hepatitis B, low = low dose HOOKVAC and high = high dose of HOOKVAC). Horizontal lines indicate 0.25, 0.50, 0.75 quantiles. HOOKVAC: Hookworm vaccine candidates comprising of Na-GST-1 and Na-APR-1 (M74).</p

DataSheet1_Choice of adjuvant and antigen composition alters the immunogenic profile of a SARS-CoV-2 subunit vaccine.PDF

Introduction: Since their introduction, adjuvanted recombinant subunit vaccines against COVID-19 have played a pivotal role in protecting global populations. Optimizing the immune response’s quality, amplitude, and durability to these vaccines depends on the appropriate adjuvant choice and dose in combination with the selected antigen.Methods: Here, we employed a preclinical mouse model to study the adaptive humoral and cellular immune responses to a SARS-CoV-2 receptor binding domain (RBD) antigen formulated with one of four different immune agonists [GLA, 3M-052, CpG-1826 (CpG), and dmLT], in combination with one of two different immune-stimulating formulations, a stabilized squalene emulsion (SE) or aluminum hydroxide (Alum). Using a weighted desirability index, we established an immunogenicity ranking for each adjuvant in combination with the RBD antigen.Results: We found that formulations of the RBD with Alum in combination with either 3M-052 or CpG led to at least a 2-log increase in serum IgG production and a 1.3- to 2.2-log increase in the number of bone marrow-derived antibody-secreting cells compared to the RBD formulated with Alum without an additional agonist. In contrast, the RBD formulated with SE in combination with 3M-052 or CpG did not elicit an IgG response greater than the unadjuvanted control. Additionally, RBD formulated with 3M-052 or CpG on Alum generated a 0.8- or 1.6-log lower splenocyte IL-5 response (a pro-Th2 marker), respectively, than Alum without an additional agonist. When formulated with 3M-052-Alum, a bivalent vaccine containing the original lineage (Wuhan-Hu-1) and the Delta variant (B.1.617.2) RBD antigens led to a more than 2-log increase in neutralizing antibodies against an Omicron variant (B.1.1.529) pseudovirus in vaccinated animals compared to animals that received the monovalent RBD antigen.Discussion: Our results suggest that optimal immune responses to subunit antigens may be achieved through an orthogonal approach that applies adjuvant formulation, antigen combination, and advances in rational vaccine development techniques.</p