Low birthweight and prematurity, but not malaria chemoprevention, are associated with reduced pneumococcal vaccine immunogenicity in Ugandan infants
Kenneth Musinguzi, Alyssa N Sbarra, Florian Bach, Felistas Nankya, Karen Bino Achom, Caroline Mwubaha, Patience Nayebare, Evelyn Nansubuga, Abel Kakuru, Jimmy Kizza, Zedekiah Maato, Emmanuel Arinaitwe, Kathleen Dantzler Press, Bernard Ssentalo Bagaya, Stephen Tukwasibwe, Isaac Ssewanyana, Joaniter Immaculate Nankabirwa, Moses Robert Kamya, Grant Dorsey, Saki Takahashi, Prasanna JagannathanAbstract
Background
Malaria exposure has been hypothesized to alter immune responses to childhood vaccines, but evidence is inconsistent. We evaluated whether early-life malaria exposure and perennial malaria chemoprevention (PMC) modify antibody responses to the 10-valent pneumococcal conjugate vaccine (PCV-10) among infants in a high malaria transmission setting in eastern Uganda.
Methods
This study was nested within the MIC-DroP trial (NCT04978272) whereby 202 infants were selected for inclusion. Serotype-specific IgG concentrations were measured using an in-house multiplex seroassay from samples obtained at 8 and 24 weeks of age. Immunogenicity was quantified as the log10 fold-change in IgG concentration between the 8 and 24-week timepoints, and seroconversion as ≥0.35 μg/mL at week 24 (i.e., seropositive). Generalized estimating equation models were used to assess associations of PCV-10 immunogenicity and seroconversion with malaria exposure, malaria chemoprevention and birth outcomes.
Results
Among the 195 of 202 infants who completed the three-dose PCV-10 series, neither infant PMC nor malaria exposure from study enrollment to 14 weeks were associated with PCV-10 immunogenicity or seroconversion. In contrast, low birthweight (<2500g) was associated with lower immunogenicity (82% lower [95% confidence interval (CI): 43-94%] antibody fold-change, p=0.003) and reduced odds of seroconversion (OR=0.19 [95% CI: 0.06-0.57], p=0.003); preterm birth (<37 weeks) showed similar associations (79% lower [95% CI: 24-94%] antibody fold-change, p=0.018; OR=0.181 [95% CI: 0.05-0.65], p=0.009).
Conclusion
In this malaria-endemic setting, early-life malaria exposure and chemoprevention did not measurably alter PCV-10 antibody responses. However, low birthweight and prematurity were associated with reduced vaccine immunogenicity.