Analysis of relationships between polymorphisms in the genes encoding the pentameric complex and neutralization of clinical cytomegalovirus isolates

Vaccine
Ryo KobayashiNaoki Inoue

Abstract

As congenital cytomegalovirus (CMV) infection is one of the major causes of birth defects and developmental abnormalities, it is essential to develop vaccines and therapeutic antibodies against CMV. Clinical trials demonstrated that the subunit vaccine based on glycoprotein B, which had been believed to be the major target for neutralization, did not induce sufficient protective immunity. On the other hand, it has been reported that the immunization of animals with the Pentamer, the pentameric complex of gH/gL/UL128/UL130/UL131A, induced strong neutralizing antibodies. Here, we sought to clarify whether any polymorphic alterations present in the Pentamer of clinical isolates affect neutralization by anti-Pentamer antibodies. Sequences of the genes encoding the Pentamer components of 25 Japanese clinical isolates were determined. Neutralization of infection by two seropositive sera and by anti-Pentamer serum was measured using a CMV reporter cell line based on ARPE-19. Polymorphisms of the amino acid sequence of UL128, UL130, and UL131A ORFs were limited and clustered into two major groups. The identified alterations, except UL128 I140T, were mapped outside of the reported regions recognized by neutralizing antibodies. Anti-Pent...Continue Reading

Citations

Aug 5, 2020·Investigative Ophthalmology & Visual Science·Nozomi IgarashiMakoto Aihara
Nov 30, 2018·International Journal of Molecular Sciences·Kenji Tanimura, Hideto Yamada

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