Biology subjects

Jimenez, L. M.

Publications and source records attributed to Jimenez, L. M..

3 recordsLinked to original sources

bioRxiv2026

Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge

Herpes simplex virus (HSV) has extensive strategies to evade host defense, including mechanisms that limit clearance by the complement cascade. Using Fc engineering, we incorporated a complement-enhancing (E430G, EG) or a complement-abrogating mutation (K322A, KA) to a panel of glycoprotein D- and glycoprotein B-specific monoclonal antibodies (mAbs) to assess the role of complement-driven antiviral activity in a neonatal mouse HSV-1 infection model. In vitro characterization confirmed that Fc modifications preserved antigen recognition while selectively amplifying or reducing complement activity. In vivo, complement modulation altered the protective capacity of select mAbs to protect against lethal HSV-1 challenge, demonstrating that complement contributes to antibody-mediated control of HSV-1 infection in an antibody- and antigen-dependent manner. The differential effects observed across the mAb panel indicate that complement activity does not function as a uniform determinant of antibody efficacy, but instead operates in concert with antibody-specific properties to shape antiviral protection. Collectively, these findings establish complement-mediated activity as an important component of antibody function in HSV-1 infection, and highlight Fc engineering as a strategy to optimize antibody-mediated protection. More broadly, these findings underscore the multifaceted nature of antibody-mediated protection and provide a mechanistic framework for considering complement-dependent functions in the development of antibody-based therapeutics.

immunology↗

bioRxiv2025

Antibodies targeting HSV glycoprotein B require effector functions to protect neonatal mice

Glycoprotein B (gB) serves as the viral fusion protein for herpes simplex virus (HSV), mediating fusion between viral and host membranes resulting in infection. As such, gB represents a potentially critical target for the host immune system with high potential relevance for vaccine design. Here we investigated the mechanisms of protection for a panel of gB-specific monoclonal antibodies (mAb) in a mouse model of neonatal HSV (nHSV) infection. Viral neutralization contributed, but Fc effector functions were critical for mAb-mediated protection against nHSV mortality, depending on dose. Moreover, AAV-mediated in vivo expression of a gB-specific mAb in mice provided transgenerational protection against HSV-1 and HSV-2 mortality in their offspring. These findings demonstrate that antibodies targeting gB can serve as potent therapeutics and that they require diverse functional profiles to afford optimal protection, informing vaccine design.

immunology↗

bioRxiv2021

Estimating the fundamental niche: accounting for the uneven1availability of existing climates

Studies that question important conceptual and methodological aspects of the field of ecological niche modeling (and species distribution modeling) have cast doubts on whether it is possible to estimate the fundamental niche of a species using presence-only data. The main limitation in niche estimation is that presence data come from the realized niche, which is only a subset of the fundamental niche. Most of the existing methods lack the ability to overcome this limitation and therefore fit niches that resemble the realized niche. To obtain a more accurate estimate of the fundamental niche, we propose using the geographic region that is accessible to a species (based on its dispersal ability) to determine a sampling distribution, in environmental space, from which we can quantify the likelihood of observing a particular environmental combination in a sample of presence points. We incorporate this sampling distribution into a multivariate normal model (i.e., a Mahalanobis distance model) by creating a weight function that modifies the probabilities of observing different environmental combinations in a sample of presences. This modification accounts for the uneven availability of environmental conditions. We show that the parameters of this weighted-normal model can be approximated with a maximum likelihood estimation approach; and then used to draw ellipsoids (confidence regions) that represent the fundamental niche of the species. We illustrate the application of our model with two worked examples. First, we use presence data for an invasive species and an accessible area that includes only its native range to evaluate whether the fitted model predicts confirmed establishments of the species outside its native range. Second, we use presence data for closely related species with known accessible areas to demonstrate how the different dispersal abilities of the species constrain a classic Mahalanobis distance model. Overall, we show that accounting for the distribution of environmental conditions that are accessible to a species indeed affects the estimation of the ellipsoids used to model its fundamental niche.

ecology↗