CORRESPONDENCE • JID 2017:216 (15 August) • 502 The Journal of Infectious Diseases Effect of an Early Dose of Measles Vaccine on Morbidity Between 18 Weeks and 9 Months of Age: A Randomized, Controlled Trial in Guinea-Bissau To the Editor—We read with inter- est the article by Do et al [1] demon- strating the efect of an early dose of measles vaccine at age 4.5 months on infant morbidity. Te authors observed that infants who received the mea- sles vaccine at 4.5 months of age had a lower hazard for diarrhea (hazard ratio [HR] = 0.89; 95% confdence interval [CI] = .82–.97), vomiting (HR = 0.86; 95% CI = .75–.98), and reported fever (HR = 0.93; 95% CI = .87–1.00) between 4.5 and 9 months of age than the infants who did not receive early measles vac- cination [1]. Fever, diarrhea, and vomit- ing are common clinical manifestations of acute infammatory episodes, and lower hazard ratios of these could sug- gest that early measles vaccination dampens subsequent general infamma- tory responses. In this regard, we have observed that higher levels of opsonized attenuated measles virus (MV) stim- ulated higher plasmacytoid dendritic cell (pDC) transforming growth factor β (TGF-β)/interferon α (IFN-α) molar ratios compared with lower levels of opsonized attenuated MV and MV alone (Figure 1). Transforming growth fac- tor β is an anti-infammatory cytokine produced by pDCs [2, 3], and IFN-α is an infammatory cytokine that is also produced by pDCs [3]. When infants are vaccinated at age 4.5 months, the circulating levels of maternally derived anti-MV immunoglobulin G (IgG) and the opsonization of attenuated MV upon measles vaccination could be more likely to promote higher anti-infammatory/ infammatory cytokine ratios compared with when measles vaccination occurs at a later age. One potential immunologi- cal mechanism by which a heightened general anti-infammatory response and a dampened infammatory response could be sustained over approximately 4.5 months is MV-induced epigenetic efects on innate immune cells (trained immunity) [4]. Our data support a potential immunological mechanism by which early measles vaccination in the presence of high circulating levels of maternally derived anti-MV IgG could dampen subsequent infant infamma- tory responses. Tis could underlie the observation by Do et al [1] that there were lower rates of fever, diarrhea, and vomiting among infants vaccinated with the measles vaccine at age 4.5 months old compared with those not vaccinated at 4.5 months of age. CORRESPONDENCE 1000 100 10 pDC TGF-β/IFN-α molar ratio 1 0.1 0.01 Measles virus (MOI=0.5) – – – + + 1/8 1/32 1/128 1/512 1/2048 1/8192 1/32 768 + + + + + + Serum dilution Figure 1. Higher levels of anti-measles virus (MV) immunoglobulin G (IgG)/MV immune complexes (opsonized MV) stimulate higher transforming growth factor β (TGF-β)/ interferon α (IFN-α) molar ratios from human plasmacytoid dendritic cells (pDCs) compared with lower levels of anti-MV IgG/MV immune complexes and MV alone. Dilutions of serum from a mother containing anti-MV IgG and preincubated with attenuated MV (Edmonston vaccine strain), and attenuated MV alone, were used to stimulate MACS- isolated human pDCs × 18–24 hours. The TGF-β and IFN-α protein levels were measured in cell culture supernatants by enzyme-linked immunosorbent assay. Bars are median values. n = 3 individual pDC donors. Abbreviations: IFN-α, interferon α; MOI, multiplicity of infection; pDC, plasmacytoid dendritic cell; TGF-β, transforming growth factor β. Downloaded from https://academic.oup.com/jid/article/216/4/502/3935090 by guest on 06 February 2023