Natalie D. Collins

Walter Reed Army Institute of Research

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Jun Hang

Walter Reed Army Institute of Research

Kayvon Modjarrad

Walter Reed Army Institute of Research

Robert A. Kuschner

Walter Reed Army Institute of Research

Christian Fung

University of Freiburg

Yu Yang

Huazhong Agricultural University

Jerry J. Hughes

Walter Reed Army Institute of Research

Anima Adhikari

Walter Reed Army Institute of Research

Anthony C Fries

United States Air Force

Adam R. Pollio

Walter Reed Army Institute of Research

Steven G. Widen

The University of Texas Medical Branch at Galveston

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Walter Reed Army Institute of Research

107

Henry M. Jackson Foundation

Jackson Foundation

National Institutes of Health

The University of Texas Medical Branch at Galveston

York District Hospital

Redeemer's University

National Institute of Allergy and Infectious Diseases

Beth Israel Deaconess Medical Center

Naval Medical Research Unit Six

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Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day

Current Infectious Disease Reports (2017)

Natalie D. Collins Alan D.T. Barrett

Yellow fever vaccine

Attenuated vaccine

Economic shortage

10.1007/s11908-017-0566-9

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Citations (107)

SARS-CoV-2 show no infectivity at later stages in a prolonged COVID-19 patient despite positivity in RNA testing

medRxiv (Cold Spring Harbor Laboratory) (2021)

Xiu‐Feng Wan Cynthia Y. Tang Detlef Ritter Yang Wang Tao Li

Abstract Inpatient COVID-19 cases present enormous costs to patients and health systems. Many hospitalized patients may still test COVID-19 positive, even after resolution of symptoms. Thus, a pressing concern for clinicians is the safety of discharging these asymptomatic patients if they have any remaining infectivity. This case report explores the viral viability in a patient with persistent COVID-19 over the course of a two-month hospitalization. Positive nasopharyngeal swab samples, analyzed by quantitative reverse transcription polymerase chain reactions (qRT-PCR), were collected and isolated in the laboratory, and infectious doses were analyzed throughout the hospitalization period. The patient experienced waning symptoms by hospital day 40 and had no viable virus growth in the laboratory by hospital day 41, suggesting no risk of infectivity, despite positive RT-PCR results, which prolonged his hospital stay. Notably, this case showed infectivity for at least 24 days from disease onset, which is longer than the discontinuation of transmission-based precautions recommendation by CDC. Thus, our findings suggest that the timeline for discontinuing transmission-based precautions may need to be extended for patients with prolonged illness. Additional large-scale studies are needed to draw definitive conclusions on the appropriate clinical management for these patients.

Infectivity

Discontinuation

10.1101/2021.03.18.21253228

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Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

Journal of Virology (2021)

Jingyou Yu Natalie D. Collins Noe B. Mercado Katherine McMahan Abishek Chandrashekar

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Postpyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage fluid. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage fluid following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that postpyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques.

2019-20 coronavirus outbreak

Coronavirus Infections

Betacoronavirus

Sars virus

10.1128/jvi.01599-21

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Citations (9)

Lassa Virus in Novel Hosts: Insights into the Epidemiology of Lassa Virus Infections in Southern Nigeria

Emerging Microbes & Infections (2023)

Anise N. Happi Olusola Ogunsanya Akeemat Opeyemi Ayinla Ayotunde E. Sijuwola Femi Mudasiru Saibu

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Lassa virus

Lassa fever

10.1080/22221751.2023.2294859

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Citations (5)

A Phase 1 Two-Arm, Randomized, Double-Blind, Active-Controlled Study of Live, Oral Plasmid-Derived Adenovirus Type 4 and Type 7 Vaccines in Seronegative Adults

Vaccines (2023)

Shannon M. Beaty Natalie D. Collins Nicos Karasavvas Robert A. Kuschner Jun Hang

PXVX0047 is an investigational vaccine developed for active immunization to prevent febrile acute respiratory disease (ARD) caused by adenovirus serotypes 4 (Ad4) and 7 (Ad7). PXVX0047 consists of a modernized, plasmid-derived vaccine that was generated using a virus isolated from Wyeth Ad4 and Ad7 vaccine tablets. A phase 1 two-arm, randomized, double-blind, active-controlled study was conducted to evaluate the safety profile and immunogenicity of the investigational adenovirus vaccines. The two components of PXVX0047 were administered orally together in a single dose to 11 subjects. For comparison, three additional subjects received the Ad4/Ad7 vaccine that is currently in use by the US military. The results of this study show that the tolerability and immunogenicity of the PXVX0047 Ad7 component are comparable with that of the control Ad4/Ad7 vaccine; however, the immunogenicity of the PXVX0047 Ad4 component was lower than expected. Clinical trial number NCT03160339.

Tolerability

10.3390/vaccines11061091

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Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines

Vaccines (2020)

Natalie D. Collins Chao Shan Bruno Tardelli Diniz Nunes Steven G. Widen Pei‐Yong Shi

Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family Flaviviridae. Candidate live-attenuated vaccine (LAV) viruses with engineered deletions in the 3' untranslated region (UTR) provide immunity and protection in animal models of ZIKV infection, and phenotypic studies show that LAVs retain protective abilities following in vitro passage. The present study investigated the genetic diversity of wild-type (WT) parent ZIKV and its candidate LAVs using next generation sequencing analysis of five sequential in vitro passages. The results show that genomic entropy of WT ZIKV steadily increases during in vitro passage, whereas that of LAVs also increased by passage number five but was variable throughout passaging. Additionally, clusters of single nucleotide variants (SNVs) were found to be present in the pre-membrane/membrane (prM), envelope (E), nonstructural protein NS1 (NS1), and other nonstructural protein genes, depending on the specific deletion, whereas in the parent WT ZIKV, they are more abundant in prM and NS1. Ultimately, both the parental WT and LAV derivatives increase in genetic diversity, with evidence of adaptation following passage.

Zika Virus

Attenuated vaccine

Flavivirus

10.3390/vaccines8020161

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Citations (3)

Seroprevalence and risk factors for Lassa virus infection in South-West and North-Central Nigeria: a community-based cross-sectional study

BMC Infectious Diseases (2024)

Abdulwasiu Bolaji Tiamiyu Olutunde Ademola Adegbite Olivia Freides Seth Frndak Samirah Sani Mohammed

Understanding the level of exposure to Lassa virus (LASV) in at-risk communities allows for the administration of effective preventive interventions to mitigate epidemics of Lassa fever. We assessed the seroprevalence of LASV antibodies in rural and semiurban communities of two cosmopolitan cities in Nigeria with poorly understood Lassa epidemiology.

Seroprevalence

Cross-sectional study

Medical microbiology

Tropical Medicine

Parasitology

Lassa fever

10.1186/s12879-024-09954-1

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Citations (0)

Attenuation of Zika Virus by Passage in Human HeLa Cells

Vaccines (2019)

Li Li Natalie D. Collins Steven G. Widen Emily H. Davis Jaclyn A. Kaiser

Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells. Therefore, it was hypothesized that wild-type ZIKV would also be attenuated after HeLa cell passaging. A human isolate from the recent ZIKV epidemic was subjected to serial HeLa cell passaging, resulting in attenuated in vitro replication in both Vero and A549 cells. Additionally, infection of AG129 mice with 10 plaque forming units (pfu) of wild-type ZIKV led to viremia and mortality at 12 days, whereas infection with 103 pfu of HeLa-passage 6 (P6) ZIKV led to lower viremia, significant delay in mortality (median survival: 23 days), and increased cytokine and chemokine responses. Genomic sequencing of HeLa-passaged virus identified two amino acid substitutions as early as HeLa-P3: pre-membrane E87K and nonstructural protein 1 R103K. Furthermore, both substitutions were present in virus harvested from HeLa-P6-infected animal tissue. Together, these data show that, similarly to other mosquito-borne flaviviruses, ZIKV is attenuated following passaging in HeLa cells. This strategy can be used to improve understanding of substitutions that contribute to attenuation of ZIKV and be applied to vaccine development across multiple platforms.

HeLa

Viremia

Zika Virus

Flavivirus

Vero cell

10.3390/vaccines7030093

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Citations (13)

A recombinant virus-like particle vaccine against adenovirus-7 induces a potent humoral response

npj Vaccines (2023)

Ryan Mazboudi Hannah Mulhall Maasz Matthew D. Resch Ke Wen Paul Gottlieb

Adenoviruses (AdVs) cause infections in humans that range from mild to severe, and can cause outbreaks particularly in close contact settings. Several human AdV types have been identified, which can cause a wide array of clinical manifestations. AdV types 4 and 7 (AdV-4 and AdV-7), which are among the most commonly circulating types in the United States, are known to cause acute respiratory disease that can result in hospitalization and rarely, death. Currently, the only vaccines approved for use in humans are live virus vaccines against AdV-4 and AdV-7, though these vaccines are only authorized for use in U.S. military personnel. While they are efficacious, use of these live virus vaccines carries considerable risks of vaccine-associated viral shedding and recombination. Here, we present an alternative vaccination strategy against AdV-7 using the virus-like particle platform (AdVLP-7). We describe the production of stable recombinant AdVLP-7, and demonstrate that AdVLP-7 is structurally analogous to wild-type AdV-7 virions (WT AdV-7). Preclinical immunogenicity studies in mice show that AdVLP-7 elicits a potent humoral immune response, comparable to that observed in mice immunized with WT AdV-7. Specifically, AdVLP-7 induces high titers of antibodies against AdV-7-specific antigens that can effectively neutralize AdV-7.

Virus-like particle

10.1038/s41541-023-00754-3

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Citations (3)

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Nature Communications (2024)

Rajeshwer S. Sankhala Kerri G. Lal Jaime L. Jensen Vincent Dussupt Letzibeth Mendez-Rivera

Abstract The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

Polyclonal antibodies

10.1038/s41467-023-44265-0

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Citations (10)