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Oral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Buchl, Michael A. Barry Dec 2007

Oral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Buchl, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …


Light-Evoked Calcium Responses Of Isolated Melanopsin- Expressing Retinal Ganglion Cells, Andrew T. E. Hartwick, Jayne R. Bramley, Jianing Yu, Kelly T. Stevens, Charles N. Allen, William H. Baldridge, Patricia J. Sollars, Gary E. Pickard Dec 2007

Light-Evoked Calcium Responses Of Isolated Melanopsin- Expressing Retinal Ganglion Cells, Andrew T. E. Hartwick, Jayne R. Bramley, Jianing Yu, Kelly T. Stevens, Charles N. Allen, William H. Baldridge, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

A small number (<2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ( [Ca2+]i ) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning). This novel approach enabled experiments on isolated ipRGCs, eliminating the potential confounding influence of rod/cone-driven input. Light induced a rise in [Ca2+]i (monitored using fura-2 imaging) in the immunopanned ipRGCs and the source of this Ca2+ signal was investigated. The Ca2+ responses were inhibited by 2-aminoethoxydiphenyl borate, SKF-96365 (1–2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole), flufenamic acid, …


Perinatal Ph And Neuropsychological Outcomes At Age 3 Years In Children Born Preterm: An Exploratory Study, Kimberly A. Espy, Theresa E. Senn, David A. Charak, Jill Tyler, Sandra A. Wiebe Nov 2007

Perinatal Ph And Neuropsychological Outcomes At Age 3 Years In Children Born Preterm: An Exploratory Study, Kimberly A. Espy, Theresa E. Senn, David A. Charak, Jill Tyler, Sandra A. Wiebe

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

The impact of extreme prematurity and related hypoxic-ischemic events on brain development recently has begun to be characterized with modern neuroimaging methods, although comparatively less is known about the neuropathology in those born at heavier birth weights. Even subclinical levels of perinatal hypoxia-ischemia, as indexed by perinatal blood pH, are related to intelligence in school-aged children born preterm. Given the impact of hypoxia-ischemia on white matter and the emerging evidence of specific executive and mathematic deficits in children born preterm, the impact of perinatal hypoxia-ischemia on these outcomes was explored in children at relatively low-risk for sequelae. In a sample …


A Bayesian Multilevel Modeling Approach For Data Query In Wireless Sensor Networks, H. Wang, H. Fang, K. A. Espy, D. Peng, H. Sharif Nov 2007

A Bayesian Multilevel Modeling Approach For Data Query In Wireless Sensor Networks, H. Wang, H. Fang, K. A. Espy, D. Peng, H. Sharif

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

In power-limited Wireless Sensor Network (WSN), it is important to reduce the communication load in order to achieve energy savings. This paper applies a novel statistic method to estimate the parameters based on the realtime data measured by local sensors. Instead of transmitting large real-time data, we proposed to transmit the small amount of dynamic parameters by exploiting both temporal and spatial correlation within and between sensor clusters. The temporal correlation is built on the level-1 Bayesian model at each sensor to predict local readings. Each local sensor transmits their local parameters learned from historical measurement data to their cluster …


Using Confirmatory Factor Analysis To Understand Executive Control In Preschool Children: I. Latent Structure, S. A. Wiebe, K. A. Espy, D. Charak Nov 2007

Using Confirmatory Factor Analysis To Understand Executive Control In Preschool Children: I. Latent Structure, S. A. Wiebe, K. A. Espy, D. Charak

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Although many tasks have been developed recently to study executive control in the preschool years, the constructs that underlie performance on these tasks are poorly understood. In particular, it is unclear whether executive control is comprised of multiple, separable cognitive abilities (e.g., inhibition and working memory) or whether it is unitary in nature. A sample of 243 normally developing children between 2.25 and 6 years of age completed a battery of age appropriate executive control tasks. Confirmatory factor analysis (CFA) was used to compare multiple models of executive control empirically. A single-factor, general model was sufficient to account for the …


Gene Family Encoding The Major Toxins Of Lethal Amanita Mushrooms, Heather E. Hallen-Adams, Hong Luo, John S. Scott-Craig, Jonathan D. Walton Nov 2007

Gene Family Encoding The Major Toxins Of Lethal Amanita Mushrooms, Heather E. Hallen-Adams, Hong Luo, John S. Scott-Craig, Jonathan D. Walton

Heather Hallen-Adams Publications

Amatoxins, the lethal constituents of poisonous mushrooms in the genus Amanita, are bicyclic octapeptides. Two genes in A. bisporigera, AMA1 and PHA1, directly encode α-amanitin, an amatoxin, and the related bicyclic heptapeptide phallacidin, a phallotoxin, indicating that these compounds are synthesized on ribosomes and not by nonribosomal peptide synthetases. α-Amanitin and phallacidin are synthesized as proproteins of 35 and 34 amino acids, respectively, from which they are predicted to be cleaved by a prolyl oligopeptidase. AMA1 and PHA1 are present in other toxic species of Amanita section Phalloidae but are absent from nontoxic species in other sections. …


Enhancement Of Efficacy Of Prrsv Vaccines By Altering The Glycosylation Pattern Of Viral Glycoproteins, Asit K. Pattnaik Oct 2007

Enhancement Of Efficacy Of Prrsv Vaccines By Altering The Glycosylation Pattern Of Viral Glycoproteins, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

PRRSV, the causative agent of PRRS is of major economic significance to the pork industry in the USA and around the world. Current commercial vaccine does not provide adequate protection against PRRSV outbreaks. Therefore, there is an urgent need for development of more efficacious vaccine to combat PRRS. Our previous studies have suggested that (i) induction of neutralizing antibody response is an important correlate of evaluating the efficacy of a vaccine; (ii) neutralizing antibodies can be enhanced by hypoglycosylation of the major surface glycoprotein (GP5). While it is known that GP5 plays a prominent role in neutralizing antibody induction, it …


A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes Sep 2007

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the …


Low Molecular Weight Protein Tyrosine Phosphatase (Lmw-Ptp) And Its Possible Physiological Functions Of Redox Signaling In The Eye Lens, Kuiyi Xing, Ashraf Raza, Stefan Lofgren, M. Rohan Fernando, Ye-Shih Ho, Marjorie F. Lou Aug 2007

Low Molecular Weight Protein Tyrosine Phosphatase (Lmw-Ptp) And Its Possible Physiological Functions Of Redox Signaling In The Eye Lens, Kuiyi Xing, Ashraf Raza, Stefan Lofgren, M. Rohan Fernando, Ye-Shih Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Low molecular weight protein tyrosine phosphatase (LMW-PTP) was cloned from human lens epithelial B3 cells (HLE B3) and the recombinant enzyme was purified to homogeneity. The pure enzyme reacted positively with anti-LMW-PTP antibody, displayed tyrosine-specific phosphatase activity and was extremely sensitive to H2O2. The inactivated LMW-PTP could be regenerated by thioltransferase (TTase)/GSH system as demonstrated by both activity assay and by mass spectrometry (MS). The MS study also showed that an intramolecular disulfide bond was formed between C13 and C18 at the active site, and was reduced by the TTase/GSH system. The putative role of LMW-PTP in regulating platelet derived …


The Neural Correlates Of Inhibitory Control In Preschool Children: Go/No-Go Task Demands Influence Erp Amplitude And Latency, S. A. Wiebe, D. J. Carroll, S. Raber, K. A. Espy May 2007

The Neural Correlates Of Inhibitory Control In Preschool Children: Go/No-Go Task Demands Influence Erp Amplitude And Latency, S. A. Wiebe, D. J. Carroll, S. Raber, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

No abstract provided.


Genetic Factors In Preschool Executive Control: Relations Between Serotonin Genotype, Working Memory, And Set Shifting, S. A. Wiebe, M. Y. Chang, A. R. Johnson, J. Huggenvik, T. Jameson, K. A. Espy Mar 2007

Genetic Factors In Preschool Executive Control: Relations Between Serotonin Genotype, Working Memory, And Set Shifting, S. A. Wiebe, M. Y. Chang, A. R. Johnson, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

No abstract provided.


Genes And Behavior In Preschool Children: The Relation Between Dopamine Genotype And Latent Executive Control, S. A. Wiebe, M. J. Moehr, A. R. Johnson, M. Y. Chang, J. Huggenvik, T. Jameson, K. A. Espy Feb 2007

Genes And Behavior In Preschool Children: The Relation Between Dopamine Genotype And Latent Executive Control, S. A. Wiebe, M. J. Moehr, A. R. Johnson, M. Y. Chang, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Objective: Dopaminergic neurotransmission is implicated in the executive control of cognition and behavior (Braver & Cohen, 2000). Presence or absence of particular dopamine gene alleles relates to executive control performance (Casey, 2002; Roesch-Ely, 2005) and to attention problems and ADHD (Durston, 2005; Schmidt, 2001). The present study examined the relation between dopamine genotype and executive control in normally-developing preschool children. Participants and Methods: The sample included 133 children (66 girls; mean age 4 years, range 2;2-6 years). Children completed a battery of executive control tasks, and were genotyped for 4 dopamine genes: the dopamine receptors DRD2 and DRD4, the dopamine …


Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo Jan 2007

Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo

Jay Reddy Publications

Myelin proteolipid protein (PLP) 139–151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2s SJL/J mice. While PLP 139–151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically reduced on the H-2s congenic B10.S background. On this resistant background, we observed a high frequency of positively selected tg CD42CD82 (DN) thymocytes and peripheral DN tg T cells. Splenic DN tg T cells responded to anti-CD3 stimulation similarly to CD41 cells, but proliferative and cytokine responses to PLP 139–151 were blunted, implying that CD4 coreceptor down-regulation modulated …


Su.32. Myelin-Specific Regulatory T Cells Accumulate In The Central Nervous System, But Fail To Suppress Pathogenic Effector T Cells At The Peak Of Autoimmune Inflammation [Abstract Only], Thomas Korn, Mohamed Oukka, Jay Reddy, Estelle Betelli, Amit Awasthi, Raymond Sobel, Kai Wucherpfennig, Vijay K. Kuchroo Jan 2007

Su.32. Myelin-Specific Regulatory T Cells Accumulate In The Central Nervous System, But Fail To Suppress Pathogenic Effector T Cells At The Peak Of Autoimmune Inflammation [Abstract Only], Thomas Korn, Mohamed Oukka, Jay Reddy, Estelle Betelli, Amit Awasthi, Raymond Sobel, Kai Wucherpfennig, Vijay K. Kuchroo

Jay Reddy Publications

Treatment with ex vivo generated regulatory T cells (Treg) has been regarded as highly attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp “knock-in” mice and myelin oligodendrocyte glycoprotein (MOG)35–55/IAb tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Following immunization with the encephalitogenic peptide MOG35–55 emulsified in complete Freund's adjuvant, MOG35–55-tetramer-reactive, Foxp3+ T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent …


Differential Engagement Of Tim-1 During Activation Can Positively Or Negatively Costimulate T Cell Expansion And Effector Function, Vijay K. Kuchroo, Sheng Xiao, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Eric Jensen, Jaimie Imitola, Thomas Korn, Ana C. Anderson, Zheng Zhang, Cristina Gutierrez, Thomas Moll, Raymond A. Sobel, Dale T. Umetsu, Hideo Yagita, Hisaya Akiba, Terry Strom, Mohamed H. Sayegh, Rosemarie H. Dekruyff, Samia J. Khoury Jan 2007

Differential Engagement Of Tim-1 During Activation Can Positively Or Negatively Costimulate T Cell Expansion And Effector Function, Vijay K. Kuchroo, Sheng Xiao, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Eric Jensen, Jaimie Imitola, Thomas Korn, Ana C. Anderson, Zheng Zhang, Cristina Gutierrez, Thomas Moll, Raymond A. Sobel, Dale T. Umetsu, Hideo Yagita, Hisaya Akiba, Terry Strom, Mohamed H. Sayegh, Rosemarie H. Dekruyff, Samia J. Khoury

School of Veterinary and Biomedical Sciences: Faculty Publications

It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specifi c for Tim-1 and identifi ed two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specifi c T cells, the production of the proinfl ammatory cytokines IFN-γ and IL-17, …


Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman Jan 2007

Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Barrier to autointegration factor (BAF) is a DNA-binding protein found in the nucleus and cytoplasm of eukaryotic cells that functions to establish nuclear architecture during mito-sis. Herein, we demonstrate a cytoplasmic role for BAF in host defense during poxviral infections. Vaccinia is the prototypic poxvirus, a family of DNA viruses that replicate ex-clusively in the cytoplasm of infected cells. Mutations in the vaccinia B1 kinase (B1) com-promise viral DNA replication, but the mechanism by which B1 achieves this has remained elusive. We now show that BAF acts as a potent inhibitor of poxvirus replication unless its DNA-binding activity is blocked …


Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski Jan 2007

Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5α. We modeled the structure of the B-box 2 domain of TRIM5α based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5αhu or rhesus monkey TRIM5αrh. However, alteration of arginine 119 of TRIM5αhu or the corresponding arginine 121 of TRIM5αrh diminished the abilities of …


Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski Jan 2007

Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …


Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt Jan 2007

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …


Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry Jan 2007

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …