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Maxfield, Lori

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Maxfield

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Lori

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Maxfield, Lori

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2015 - 20183

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Author's Publications: search.filters.isAuthorOfPublication.eed4ac7c-affd-4cbc-a3e9-5e5e14c37332

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    Vaccine Protection Against Zika Virus from Brazil
    (2016) Larocca, Rafael; Abbink, Peter; Peron, Jean Pierre S.; de A. Zanotto, Paolo M.; Iampietro, M. Justin; Badamchi-Zadeh, Alexander; Boyd, Michael; Ng’ang’a, David; Kirilova, Marinela; Nityanandam, Ramya; Mercado, Noe B.; Li, Zhenfeng; Moseley, Edward T.; Bricault, Christine; Borducchi, Erica N.; Giglio, Patricia B.; Jetton, David; Neubauer, George; Nkolola, Joseph; Maxfield, Lori; De La Barrera, Rafael A.; Jarman, Richard G.; Eckels, Kenneth H.; Michael, Nelson L.; Thomas, Stephen J.; Barouch, Dan
    Zika virus (ZIKV) is a flavivirus that is responsible for an unprecedented current epidemic in Brazil and the Americas1,2. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans3–8 and mice9–11. The rapid development of a safe and effective ZIKV vaccine is a global health priority1,2, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization of a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a ZIKV outbreak strain from northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice11. We produced DNA vaccines expressing full-length ZIKV pre-membrane and envelope (prM-Env) as well as a series of deletion mutants. The full-length prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV as measured by absence of detectable viremia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and CD4 and CD8 T lymphocyte depletion in vaccinated mice did not abrogate protective efficacy. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.
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    Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization
    (American Society for Microbiology, 2015) Maxfield, Lori; Abbink, Peter; Stephenson, Kathryn; Borducchi, Erica N.; Ng'ang'a, David; Kirilova, Marinela M.; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan
    Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors.
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    Rapid Cloning of Novel Rhesus Adenoviral Vaccine Vectors
    (American Society for Microbiology, 2018) Abbink, Peter; Kirilova, Marinela; Boyd, Michael; Mercado, Noe; Li, Zhenfeng; Nityanandam, Ramya; Nanayakkara, Ovini; Peterson, Rebecca; Larocca, Rafael; Aid, Malika; Tartaglia, Lawrence; Mutetwa, Tinaye; Blass, Eryn; Jetton, David; Maxfield, Lori; Borducchi, Erica N.; Badamchi-Zadeh, Alexander; Handley, Scott; Zhao, Guoyan; Virgin, Herbert W.; Havenga, Menzo J.; Barouch, Dan
    ABSTRACT Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5. However, baseline immunity to these vectors still exists in human populations. Traditional cloning of new adenovirus vaccine vectors is a long and cumbersome process that takes 2 months or more and that requires rare unique restriction enzyme sites. Here we describe a novel, restriction enzyme-independent method for rapid cloning of new adenovirus vaccine vectors that reduces the total cloning procedure to 1 week. We developed 14 novel adenovirus vectors from rhesus monkeys that can be grown to high titers and that are immunogenic in mice. All vectors grouped with the unusual adenovirus species G and show extremely low seroprevalence in humans. Rapid cloning of novel adenovirus vectors is a promising approach for the development of new vector platforms. Rhesus adenovirus vectors may prove useful for clinical development. IMPORTANCE: To overcome baseline immunity to human and chimpanzee adenovirus vectors, we developed 14 novel adenovirus vectors from rhesus monkeys. These vectors are immunogenic in mice and show extremely low seroprevalence in humans. Rhesus adenovirus vectors may prove useful for clinical development.