#26: Investigating CMV Pathogenesis and Breast Milk Transmission In Premature Infants Who Acquire Symptomatic CMV Viremia

Background CMV can be transmitted to babies after birth through breast milk and such infections may lead to a “sepsis-like syndrome” with neutropenia, hepatitis, and viremia. CMV infections can be epidemiologically characterized by envelope glycoprotein (gB) genotypes - gB1, gB2, gB3 and gB4. The role of specific genotypes in pathogenesis and immune control of infection is incompletely characterized. These studies aimed to characterize viral and host correlates of breast-milk transmission of CMV in a neonatal intensive care unit (NICU) setting. Methods 200 infants were enrolled in a prospective study of infants <1500 grams at birth in the NICU at the University of MN Masonic Children’s Hospital. Breast milk samples were available from 164 mothers, representing 184 infants (including twin pairs). We compared CMV IgM titer (Gold Standard Diagnostics Corp, CA) and CMV IgG titer (Diamedix, FL) in non-viremic infants of seropositive mothers for whom we had available serum (n=48 infants), and in eight infants with DNAemia. Positive CMV Breast milk samples from 65 mothers were further characterized by a multiplex real-time PCR assay, to characterize and compare gB genotypes. Results The prevalence of DNAlactia in the breast milk was 65/150 (43%). There were 49 mothers for whom CMV was present in breast milk, for which we also had infant whole blood samples (58 infants; 40 singletons and 9 twin pairs). Eight infants, exposed to CMV in the breast milk, developed CMV viremia (8/58=13%). Clinicians had not tested for CMV in 5/8 cases. Anti-CMV IgM antibodies were detected in 6/8 (75%) viremic infants. One non-viremic infant with CMV infection was identified solely by the IgM assay. There was no difference in ELISA IgG titers between infants with CMV viremia, and nonviremic infants. The subset of 65 CMV positive breast milk samples, 25 were positive for gB1 (39%), 13 were positive for gB2 (20%), 23 were positive for gB3 (35%) and 11 were positive for gB4 (17%); 11 samples were positive for multiple gB genotypes. For six samples, the gB genotype was unable to be determined. The gB genotype was determined for 5 of eight breast milk samples from mothers of the viremic babies with gB1 being the most common. In 3 of the 8 viremic samples, genotype was unable to be determined. Conclusion Breast milk from CMV-seropositive lactating mothers in a NICU setting can lead to transmission of infection and development of symptomatic CMV disease, which may not be recognized by clinicians. The distribution of gB genotypes in breast milk is similar to that observed in other CMV epidemiological analyses, and multiple genotypes may be identified in lactating seropositive women. Since gB is a critical target in CMV vaccine design, understanding strain-specific transmission may have implications for understanding the impact of pre-pregnancy vaccination on breast milk transmission. Purified recombinant gB vaccines studied in clinical trials are based on based on the Towne strain of CMV, gB1 genotype (DOI: 10.1128/JVI.01695-18). Future studies should examine the impact of strain-specificity of vaccination on circulation of CMV strains in infants with CMV disease.

Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques

ABSTRACT Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV envelope (Env) protein only, (ii) poxvirus vector (modified vaccinia virus Ankara [MVA])-HIV Env prime and HIV Env boost, and (iii) coadministration of HIV Env and MVA-HIV Env at all time points. The vaccines were administered with an accelerated, 3-week-interval regimen starting at birth for early induction of highly functional HIV Env-specific antibodies. We also tested whether an extended, 6-week immunization interval using the same vaccine regimen as in the coadministration group would enhance the quality of antibody responses. We found that pediatric HIV vaccines administered at birth are effective in inducing HIV Env-specific plasma IgG. The vaccine regimen consisting of only HIV Env protein induced the highest levels of variable region 1 and 2 (V1V2)-specific antibodies and tier 1 neutralizing antibodies, whereas the extended-interval regimen induced both persistent Env-specific systemic IgG and mucosal IgA responses. Antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies in plasma were elicited by all vaccine regimens. These data suggest that infant immunizations beginning at birth are effective for the induction of functional HIV Env-specific antibodies that could potentially protect against breast milk transmission of HIV and set the stage for immunity prior to sexual debut.

ACUTE TOXOPLASMOSIS IN A BREASTFED INFANT WITH POSSIBLE TRANSMISSION BY WATER

Toxoplasma gondii transmission via breastfeeding has been discussed; however, no cases have been confirmed to date. This article describes a case of acute toxoplasmosis diagnosed in a mother and her six-month-old breastfed infant. The study accounts for the possibility of breast milk transmission and directs both clinicians and pediatricians to the hypothesis that both patients acquired toxoplasmosis via water ingestion.