Viral Diversity and Neutralizing Antibody Responses in Infants with Symptomatic Congenital CMV Disease receiving Antiviral Therapy
Methods: Residual samples were available from 8 infants with symptomatic cCMV enrolled in the NIAID’s CASG 109 study, a PK study of valgancyclovir. Subjects received 6 weeks of antiviral therapy from enrollment. Blood samples obtained at enrollment (less than 3 weeks of age) and 6 months later were analyzed for genotypes of glycoproteins gB, gH and gN. Neutralization response was measured in sera at enrollment using gN recombinant viruses. A 3-fold difference in neutralizing titers against at least two gN recombinant viruses was considered evidence of strain specific response.
Results: All 8 patients had >1 CMV genotype detected at either enrollment or 6 months. At enrollment, all subjects had >1 strain detected, with a range of 2-4 strains per subject. At follow up, the number of strains for each patient ranged from 1 to 3. Five of the 8 subjects had fewer genotypes detected at 6 month follow-up compared to enrollment. Two subjects had the appearance of new strains after 6 months.
All subjects had detectible neutralization response against all 4 recombinant gN viruses (titers >400) within the first month of life. Strain-specific neutralizing responses were detected in 5 children. Although not statistically significant, lower neutralizing titers were observed in 5 children who were infected with ≤ 2 gN genotypes compared to those with greater virus diversity (mean titers, 3800 vs 4500).
Conclusion: All study infants were infected with multiple CMV strains and most had strain-specific neutralizing antibody responses. Overall the viral diversity decreased over time. It is unknown at this point if the changes in viral diversity are related to antiviral treatment. Studies are ongoing to determine strain specific neutralization over time and the association between virus diversity and antibody responses in a larger cohort randomized to longer antiviral treatment times.
S. Pati, None
D. W. Kimberlin, GSK: Grant Investigator and I served as one of dozens of study sites for clinical trials conducted by GSK. All monies went directly to my university and not to me., Grant recipient
Gilead: Grant Investigator and I served as one of dozens of study sites for clinical trials conducted by Gilead. All monies went directly to my university and not to me., Grant recipient
S. Boppana, None
S. Ross, None