1547 Modification of Maternal and Congenital Cytomegalovirus Infection by Anti–Glycoprotein B Antibody Transfer in Guinea Pigs Archana Chatterjee, 1 Christopher J. Harrison, 2 William J. Britt, 4 and Chhanda Bewtra 3 1 Creighton University and 2 University of Nebraska Medical Center, Combined Division of Pediatric Infectious Diseases, and 3 Department of Pathology, Creighton University, Omaha, Nebraska; 4 Division of Pediatric Infectious Diseases, University of Alabama, Birmingham Prepregnancy human and guinea pig cytomegalovirus immunity reduces rates of congenital infection in subsequent pregnancies. Inbred JY-9 strain guinea pigs were used to study the role of hyperimmune anti–glycoprotein B (gB) serum in modification of congenital infection in early pregnancy. Significantly shorter duration of primary maternal viremia and fewer pregnancy losses occurred in passively immunized dams, compared with nonimmune dams. Placentas from recipients of negative control serum were smaller and had marked mononuclear cell infiltrates and focal necrosis and more viral foci than did those from recipients of anti- gB hyperimmune serum. Significantly higher intrauterine growth retardation occurred in pups of negative control serum recipients than in pups of passively immunized dams. Significantly higher proportions of pups and placentas from recipients of negative control serum were positive on viral culture than from passively immunized dams. Thus, anti-gB passive im- munization decreased fetal infection and intrauterine growth retardation, shortened maternal viremia, and reduced pregnancy losses and placental inflammation and infection. Human (H) cytomegalovirus (CMV) is the most common cause of congenital infection in humans, occurring in ∼1%–2% of all live US births [1]. Vertical transmission is reduced from 35%–50% with primary gestational infection to 0.2%–2% in mothers with prepregnancy HCMV antibody as a marker of previous CMV infection [2]. Severe symptoms occur in 10%–15% of congenitally infected infants of mothers lacking prepregnancy HCMV immunity, compared with !1% of infants born to mothers with prepregnancy HCMV immunity [3]. Con- genitally infected infants born to CMV-infected women with preconception seroimmunity also have more-favorable long- term outcomes and less frequently develop long-term central nervous system sequelae [2]. A recent study, however, demon- strated no significant differences in the incidence of sequelae at long-term follow-up between children born to women with re- current infection and those born to women with primary ma- ternal infection [4]. The relative contributions of specific components of maternal immune responses associated with fetal protection in women with preconception seroimmunity are not fully understood. Received 22 December 2000; revised 1 March 2001; electronically pub- lished 27 April 2001. Presented in part: annual meeting of the Pediatric Academic Societies, New Orleans, May 1998 (abstract 821). All animal experimentation was performed in accordance with the guide- lines of the Creighton University animal review committee. Reprints or correspondence: Dr. Archana Chatterjee, 2500 California Plaza, Rm. 409, Criss II, Creighton University, Omaha, NE 68178 (achatter @creighton.edu). The Journal of Infectious Diseases 2001; 183:1547–53  2001 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2001/18311-0001$02.00 Neutralizing antibody, cell-mediated responses, a reduction in infection-induced cytokines, or a combination thereof may be responsible for the noted protective effect. All components of the immune system probably cooperate to restrict local infec- tion and maternal virus load, as well as virus load delivered to the placenta and secondary inflammatory responses. A study of mice infected with murine CMV supports the concept that both humoral and cellular immunity are important during dif- ferent phases of CMV disease [5]. Because of difficulties inherent in the investigation of the placenta in humans, a small animal model of congenital CMV infection in the guinea pig has been developed. This model allows for the investigation of the effects of primary maternal CMV infection on early pregnancy and the immature placenta and of immunologic modification during pregnancy. Many as- pects of guinea pig CMV (GPCMV) parallel HCMV in non- pregnant hosts (self-limited viremia, peripheral blood mono- nucleosis, splenomegaly, and lymphadenopathy) [6, 7]. There is also homology in the genomic organization of HCMV and GPCMV [8], guinea pig and human placentas are structurally similar [9], and the relatively long (65–70 days) guinea pig ges- tation exhibits trimester-like divisions [9]. Intrauterine trans- mission occurs in 35%–50% of offspring after primary maternal gestational infection in both guinea pigs and humans [2, 10]. Finally, cell-mediated and antiviral antibody assays are avail- able for the characterization of maternal and fetal GPCMV immune responses [11]. In this study, we investigated the effects of primary maternal GPCMV infection on early pregnancy and the immature pla- centa. We also investigated the effects of passive transfer of low- and high-titer anti–glycoprotein B (gB) antibodies administered Downloaded from https://academic.oup.com/jid/article/183/11/1547/926723 by guest on 26 December 2021