Content of review 1, reviewed on September 26, 2023

This manuscript provides information on potential vaccine candidates for consideration in setting with co-infections (P. falciparum and S. haematobium). This work answers a well-conceived research question – I applaud this. To make this manuscript and its message clear to a reader of Parasite Immunology, I have specific comments for each section of the manuscript.

Title page
Line 26. It is great Ethical approval was obtained from the IRB. Is approval from the national regulator of research in Ghana not required? Does such a regulator exist?

Abstract
Line 31. The statement “Antibody responses to malaria vaccine candidates (MVC), protect from clinical malaria and its outcomes” is refutable. Protection is not total as this may suggest.
Line 42. Inconsistent number of decimal places.
Line 43. Whenever ITN is used, do you mean “ITN use”? If so, please correct this throughout this document, in the tables too. Is it “… associated with modulation of antibody responses” or “… associated with [the measure of modulation of antibody response]? Please clarify.
Also, is it positively or negatively associated? Indicate
Line 47. The conclusion is not consistent with the results. Results talk about Pf and ITN use and how they associate with antibody responses to vaccine antigens. The conclusion should be drawn from this.

Introduction
Line 74. On the statement “….during the second trimester of pregnancy when ANC starts…” ANC starts in first trimester. Medical checkups are recommended as soon as one finds out they are pregnant and not wait for second semester as indicated here. IPTp is given at scheduled ANC visits starting in the second trimester. Please revise.
Line 75-76. IPTp with SP is contraindicated in the first trimester of pregnancy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416188/. Also see New WHO recommendations for IPTp-SP. https://www.who.int/publications/i/item/WHO-HTM-GMP-2014.4 “SP should not be given during the first trimester of pregnancy”. IPTp-SP is recommended for 2nd trimester. https://web.archive.org/web/20140305032600/http://www.who.int/malaria/areas/preventive_therapies/pregnancy/en/ Revise lines 73-76

Methods
Line 131 states the study design and not line 141-153. Rename accordingly
Line 143. “…delivery within 10 am -2 pm GMT” could be “…delivery from 10 am to 2 pm GMT”
Line 167. How about change the format from “methylotrophic yeast and was produced in Rijswijk, The Netherlands” to “methylotrophic yeast ([Company name here], Rijswijk, The Netherlands)” other antigens/reagents can follow this format (lines 167-175)
Line 168 is not complete. … was produced by the [missing company here] in Copenhagen (Denmark).

Line 215.
Table 1. For some variables in Table 1, the numbers do not add up to 337. See Education level, ITN, Gravidity. For ITN use either Yes/No but not both e.g., Yes [300/337 (89%)

Table 2: Table2 should be combined with table 1. The two share the same variables. Where they do not, place a hyphen. For the variable below; the numbers do not add up to 139. See ITN use, Gravidity
For IPTp use, consider either Yes or No e.g., Yes [125/139 (89%)

In tables 1 and 2, what are you investigating about the seasons? Is it the season of the ANC visit?

Results
Figures 1 and 2. The X axis label “Candidate_antigens” needs editing. “Malaria Vaccine Candidates” is sufficient. For visual side by side comparison, could you combine figure 1 (ANC) and figure 2 (delivery)
Line 258. “Pregnant women had significantly higher antibody responses to CSP, AMA_1 and GLURP-R0. (p=0.035, 0.001, 0,003, independent t-test) respectively”. What is the other comparison group here - Is it S. haematobium infected pregnant women vs. non-infected?
Line 262. Same as 258, comparison group (S. haematobium infected) is missing.
Line 263. Could you delete “P values (0.36, 0.30, 0.93, 0.45 and 0.70), correspond to the order presented in the graph”? The figure should show these.
Line 266-270 are showing factors associated with antibody levels to
The title is not matching that. Then Lines 270-273 are showing antibody responses to malaria candidate vaccines in women with placental infection. Revise whole section.
Line 277. No comparison group indicated (i.e., could end …. than non-infected women)
Line 281. This section is investigating factors associated with antibody responses to MVC in pregnant worm at ANC. Change title accordingly.
Line 282. For each Study hospital, Pf. infection, ITN and education, add the p-value.
Line 283. “Table 1 of supplementary data” is “Supplementary Table 1”
Table 3: “Effect of study variables on malaria vaccine antigens at ANC” is not appropriate for table. Maybe Factors associated with antibody responses at ANC?
Line 290 see comment for line 281 above.
Line 291 see comment for line 282 above.
Line 293 see comment for line 283 above.
Table 4 has no heading. Is it “Factors associated with antibody responses at Delivery”?

Discussion
Line 306. Those at ANC and those at delivery were not matched individuals to conclude a high prevalence of Pf infection at ANC before intervention with IPTp.
Line 310. “… in Adidome and Battor at ANC probably reflect a higher malaria exposure at Adidome where a higher Pf prevalence was found compared to BH” is not clear. The results do not show the separate Pf prevalence for sites AH and for BH.
Line 313. “… active Pf infection correlated”. Doesn’t qPCR pick up past infections too?
Line 317. What are non-pregnancy specific MVC? Which MVCs are pregnancy specific?
Line 333 “difference in antibody response and seasonality from our study” is not clear. needs rewriting
Line 259 “One important finding of this study was that S. haematobium modulation” How was the modulation measured?

Conclusion
Line 392 “modulation of antibody response to vaccine candidates” was not a variable in this study. It was antibody response to vaccine candidates.

Line 400. Any suggestions to mitigate the weaknesses indicated?

Funding
What is IRD (JEAI-MAHEVA), LMI CONS-HELM in full?

References
Ref 57 - The site is not secure. Maybe https://pubmed.ncbi.nlm.nih.gov/31267495/?

Supporting tables
“Mean antibody response to malaria vaccine candidates (ng/mL)” in the table is “Mean antibody levels to malaria vaccine candidates (ng/mL)” (S1 and S2)
Under Marital status, single is missing (S1)

Supporting figures
The X axis label “Candidate_antigens” needs editing. Consistent with MVC in manuscript, “Malaria Vaccine Candidates” is sufficient.
The X axis label “… titres…” should be changed to “….levels” for consistency with the text in the mauscript

Source

    © 2023 the Reviewer.

References

    Adjeley, F. N., Atikatou, M., Bright, A., Asamoah, K. K., F., O. M., Charity, A., K., A. W., Yaw, D. A., A., A. A., T., N. N., David, C. 2024. Antibody response to malaria vaccine candidates in pregnant women with Plasmodium falciparum and Schistosoma haematobium infections. Parasite Immunology.