Randomized Trial of Maternal Hyperimmune Globulin to Prevent Congenital Cytomegalovirus (CMV): 2 year outcomes

Congenital cytomegalovirus (cCMV) might occur as a result of the human cytomegalovirus (HCMV) primary (PI) or nonprimary infection (NPI) in pregnant women. Immune correlates of protection against cCMV have been partly identified only for PI. Following either PI or NPI, HCMV strains undergo latency. From a diagnostic standpoint, while the serological criteria for the diagnosis of PI are well-established, those for the diagnosis of NPI are still incomplete. Thus far, a recombinant gB subunit vaccine has provided the best results in terms of partial protection. This partial efficacy was hypothetically attributed to the post-fusion instead of the pre-fusion conformation of the gB present in the vaccine. Future efforts should be addressed to verify whether a new recombinant gB pre-fusion vaccine would provide better results in terms of prevention of both PI and NPI. It is still a matter of debate whether human hyperimmune globulin are able to protect from HCMV vertical transmission. In conclusion, the development of an HCMV vaccine that would prevent a significant portion of PI would be a major step forward in the development of a vaccine for both PI and NPI.

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A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection

New England Journal of Medicine ◽

10.1056/nejmoa1913569 ◽

2021 ◽

Vol 385 (5) ◽

pp. 436-444

Author(s):

Brenna L. Hughes ◽

Rebecca G. Clifton ◽

Dwight J. Rouse ◽

George R. Saade ◽

Mara J. Dinsmoor ◽

...

Keyword(s):

Cytomegalovirus Infection ◽

Congenital Cytomegalovirus Infection ◽

Congenital Cytomegalovirus ◽

Hyperimmune Globulin

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Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

10.1101/127647 ◽

2017 ◽

Author(s):

Cody S. Nelson ◽

Diana Vera Cruz ◽

Dollnovan Tran ◽

Kristy M. Bialas ◽

Lisa Stamper ◽

...

Keyword(s):

Fetal Loss ◽

Congenital Infection ◽

Neonatal Infection ◽

Congenital Cytomegalovirus Infection ◽

Nonhuman Primate Model ◽

Primate Model ◽

Congenital Cytomegalovirus ◽

Congenital Cmv Infection ◽

Hyperimmune Globulin ◽

Congenital Cmv

AbstractHuman cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission. Pregnant, CD4+ T cell-depleted, rhesus CMV (RhCMV)-seronegative rhesus monkeys were treated with either standardly-produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV swarm. HIG passive infusion provided complete protection against fetal loss in both groups, and the potently-neutralizing HIG additionally inhibited placental transmission of RhCMV. Our findings suggest that antibody alone at the time of primary infection can prevent congenital CMV and therefore could be a primary target of vaccines to eliminate this neonatal infection.

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