Melissa De La Garza

Bio: Melissa De La Garza is an academic researcher from Texas Biomedical Research Institute. The author has contributed to research in topics: Epilepsy & Viremia. The author has an hindex of 9, co-authored 17 publications receiving 473 citations. Previous affiliations of Melissa De La Garza include University of Texas Health Science Center at San Antonio.

Immunogenicity and protective efficacy of a recombinant subunit West Nile virus vaccine in rhesus monkeys.

Abstract: The immunogenicity and protective efficacy of a recombinant subunit West Nile virus (WNV) vaccine was evaluated in rhesus macaques (Macaca mulatta). The vaccine consisted of a recombinant envelope (E) protein truncated at the C-terminal end, resulting in a polypeptide containing 80% of the N-terminal amino acids of the native WNV protein (WN-80E), mixed with an adjuvant (GPI-0100). WN-80E was produced in a Drosophila melanogaster expression system with high yield and purified by immunoaffinity chromatography using a monoclonal antibody specific for flavivirus E proteins. Groups of monkeys were vaccinated with formulations containing 1 or 25 microg of WN-80E antigen, and both humoral and cellular immunity were assessed after vaccination. The results demonstrated potent antibody responses to vaccination, as determined by both enzyme-linked immunosorbent assay and virus-neutralizing antibody assays. All vaccinated animals responded favorably, and there was little difference in response between animals immunized with 1 or 25 microg of WN-80E. Cellular immunity was determined by lymphocyte proliferation and cytokine production assays using peripheral blood mononuclear cells from vaccinated animals stimulated in vitro with WN-80E. Cell-mediated immune responses varied from animal to animal within each group. About half of the animals responded with lymphoproliferation, cytokine production, or both. Again, there was little difference in response between animals immunized with a 1- or 25-microg dose of WN-80E in the vaccine formulations. In a separate experiment, groups of monkeys were immunized with the WN-80E/GPI-0100 vaccine or an adjuvant-only control formulation. Animals were then challenged by inoculation of wild-type WNV, and the level of viremia in each animal was monitored daily for 10 days. The results showed that whereas all animals in the control group had detectable viremia for at least 3 days after challenge, all of the vaccinated animals were negative on all days after challenge. Thus, the WN-80E vaccine was 100% efficacious in protecting monkeys against infection with WNV.

Common Marmosets {Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains

Abstract: Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log(10) PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans.

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Abstract: Reactive oxygen, nitrogen, and sulfur species, referred to as ROS, RNS, and RSS, respectively, are produced during normal cell function and in response to various stimuli. An imbalance in the metabolism of these reactive intermediates results in the phenomenon known as oxidative stress. If left unchecked, oxidative molecules can inflict damage on all classes of biological macromolecules and eventually lead to cell death. Indeed, sustained elevated levels of reactive species have been implicated in the etiology (e.g., atherosclerosis, hypertension, diabetes) or the progression (e.g., stroke, cancer, and neurodegenerative disorders) of a number of human diseases.1 Over the past several decades, however, a new paradigm has emerged in which the aforementioned species have also been shown to function as targeted, intracellular second messengers with regulatory roles in an array of physiological processes.2 Against this backdrop, it is not surprising that considerable ongoing efforts are aimed at elucidating the role that these reactive intermediates play in health and disease. Site-specific, covalent modification of proteins represents a prominent molecular mechanism for transforming an oxidant signal into a biological response. Amino acids that are candidates for reversible modification include cysteines whose thiol (i.e., sulfhydryl) side chain is deprotonated at physiological pH, which is an important attribute for enhancing reactivity. While reactive species can modify other amino acids (e.g., histidine, methionine, tryptophan, and tyrosine), this Review will focus exclusively on cysteine, whose identity as cellular target or “sensor” of reactive intermediates is most prevalent and established.3 Oxidation of thiols results in a range of sulfur-containing products, not just disulfide bridges, as typically presented in biochemistry textbooks. An overview of the most relevant forms of oxidized sulfur species found in vivo is presented in Chart 1. Open in a separate window Chart 1 Biologically Relevant Cysteine Chemotypesa aRed, irreversible modifications. Green, unique enzyme intermediates. Note: Additional modifications can form as enzyme intermediates including thiyl radicals, disulfides, and persulfides.

West Nile virus infection and immunity

Abstract: West Nile virus (WNV) is an emerging neurotropic flavivirus that is transmitted to humans through the bite of an infected mosquito. WNV has disseminated broadly in the Western hemisphere and now poses a significant public health risk. The continuing spread of WNV, combined with the lack of specific therapeutics or vaccines to combat or prevent infection, imparts a pressing need to identify the viral and host processes that control the outcome of and immunity to WNV infection. Here, we provide an overview of recent research that has revealed the virus-host interface controlling WNV infection and immunity.

Evolution in health and medicine Sackler colloquium: Evolution of the human lifespan and diseases of aging: roles of infection, inflammation, and nutrition.

Abstract: Humans have evolved much longer lifespans than the great apes, which rarely exceed 50 years. Since 1800, lifespans have doubled again, largely due to improvements in environment, food, and medicine that minimized mortality at earlier ages. Infections cause most mortality in wild chimpanzees and in traditional forager-farmers with limited access to modern medicine. Although we know little of the diseases of aging under premodern conditions, in captivity, chimpanzees present a lower incidence of cancer, ischemic heart disease, and neurodegeneration than current human populations. These major differences in pathology of aging are discussed in terms of genes that mediate infection, inflammation, and nutrition. Apolipoprotein E alleles are proposed as a prototype of pleiotropic genes, which influence immune responses, arterial and Alzheimer’s disease, and brain development.