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Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4(+) T-cell depleted at the time of inoculation. Animals that received the CD4(+) T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8(+) T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4(+) T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.

Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4+ T-cell depleted at the time of inoculation. Animals that received the CD4+ T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8+ T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4+ T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease. [ABSTRACT FROM AUTHOR]

Abstract: The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (days 5–7) before the development of classical antigen-specific CD8+ and CD4+ T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post-vaccination activated CD8+ gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4+ T cells produced IFN-γ and TNF-α at day 7 post-vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination. [ABSTRACT FROM AUTHOR]

Pharyngeal infections by Neisseria gonorrhoeae are often asymptomatic, making them difficult to treat. However, in vivo animal modeling of human pharyngeal infections by pathogenic Neisseria species is challenging due to numerous host tropism barriers. We have relied on rhesus macaques to investigate pharyngeal persistence of naturally occurring Neisseria species in response to antibiotics. These species include Neisseria mucosa , Neisseria oralis , and a species unique to macaques. Four animals previously treated intramuscularly with the fluoroquinolone enrofloxacin for 2 weeks were monitored for persistence of their preexisting Neisseria populations for a period of 10 weeks. Enrofloxacin exposure did not eliminate preexisting flora from two of the four animals. Characterization of a collection of macaque Neisseria isolates supported the hypothesis that pharyngeal persistence was linked to reduced enrofloxacin susceptibility conferred by mutations in either gyrA or parC Interestingly, we observed a change in neisserial population dynamics for several weeks following enrofloxacin exposure. Enrofloxacin appeared to promote competition between strains for dominance in the pharyngeal niche. Specifically, following enrofloxacin treatment, strains bearing single gyrA mutations and low MICs persisted long-term. In contrast, strains with both gyrA and parC mutations and high MICs became culturally undetectable, consistent with the hypothesis that they were less fit. Our study has provided insight into pharyngeal persistence dynamics of Neisseria species bearing fluoroquinolone resistance determinants. The rhesus macaque provides a valuable host animal that may be used in the future to simulate treatment failures associated with the presence of antimicrobial-resistant Neisseria spp. in the human pharynx., (Copyright © 2020 American Society for Microbiology.)

Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. In a subset of infected infants, congenital HCMV causes severe, long-lasting sequelae, including deafness, microcephaly, neurodevelopmental delay, and even death. Accordingly, a maternal vaccine to prevent congenital HCMV infection continues to be a top public health priority. Nevertheless, all vaccines tested to date have failed to meet clinical trial endpoints. Maternal immunity provides partial protection against congenital HCMV transmission, as vertical transmission from seropositive mothers is relatively rare. Therefore, an understanding of the maternal immune correlates of protection against HCMV congenital infection will be critical to inform design of an efficacious maternal vaccine. This review summarizes our understanding of the innate and adaptive immune correlates of protection against congenital transmission of HCMV, and discusses the advantages and applications of a novel nonhuman primate model of congenital CMV transmission to aid in rational vaccine design and evaluation., (Copyright © 2017 IFPA, Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.)