ASKING FOR A FRIEND
  • Home
  • What is the vaccine?
  • Purchase Book
  • Kids Book
  • Herpes 101 Podcast
  • Articles
  • T-shirts and Stickers
  • Penny Letter Campaign
  • Reader Testimonials
  • Press
  • Dr. Halford's Research
  • PDF Downloads
  • More
    • Home
    • What is the vaccine?
    • Purchase Book
    • Kids Book
    • Herpes 101 Podcast
    • Articles
    • T-shirts and Stickers
    • Penny Letter Campaign
    • Reader Testimonials
    • Press
    • Dr. Halford's Research
    • PDF Downloads
ASKING FOR A FRIEND
  • Home
  • What is the vaccine?
  • Purchase Book
  • Kids Book
  • Herpes 101 Podcast
  • Articles
  • T-shirts and Stickers
  • Penny Letter Campaign
  • Reader Testimonials
  • Press
  • Dr. Halford's Research
  • PDF Downloads

2021 Rational Vaccines Data

Click the link below for new data

Link to data

If you like to watch video lectures and read scientific papers, you will enjoy this section. Below are links to Dr. Halford's work and research on the herpes simplex virus, spanning over the last 20 years. 

These are all the reasons I have a story to tell. 


Dr. William Halford 

EDUCATION: B.S. Marine Biology and Microbiology, University of  California, Santa Barbara (1986-91); Ph.D. Viral Immunology, Louisiana  State University HSC, New Orleans (1992-96); Postdoctoral fellow,  Molecular Virology, University of Pennsylvania, Philadelphia (1997-2000) FACULTY APPOINTMENTS: Assistant Professor of Microbiology and  Immunology, Tulane University School of Medicine, New Orleans  (2000-2004); Assistant Professor of Veterinary Molecular Biology, Montana State  University, Bozeman (2004-2007); Associate Professor of Microbiology and  Immunology, Southern Illinois University School of Medicine,  Springfield (2007 - present)

 Dr Halford passed away on June 22, 2017



The work of Dr. William Halford

A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection

Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens

Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection

https://www.ncbi.nlm.nih.gov/pubmed/21412438


http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017748

Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection

Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens

Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection

https://www.ncbi.nlm.nih.gov/pubmed/23755244


http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065523

Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens

Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens

Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens

https://www.ncbi.nlm.nih.gov/pubmed/25658852


http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116091

ICP0 is required for efficient reactivation of herpes simplex virus type 1

The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus

Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens


https://www.ncbi.nlm.nih.gov/pubmed/11238850


http://jvi.asm.org/content/75/7/3240

The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus

The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus

The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus

https://www.ncbi.nlm.nih.gov/pubmed/11886249


https://www.sciencedirect.com/science/article/pii/S0042682201912802?via%3Dihub

ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus:

The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus

The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus


https://www.ncbi.nlm.nih.gov/pubmed/16764725


https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-3-44


Impact of Type I Interferon on theSafety and Immunogenicity

Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

Viral fitness dictates virulence and capacity to evade host immune de-fenses. Understanding the biological underpinnings of such features is essential forrational vaccine development. We have previously shown that the live-attenuatedherpes simplex virus 1 (HSV-1) mutant lacking the nuclear localization signal (NLS)on the ICP0 gene (0ΔNLS) is sensitive to inhibition by interferon beta (IFN-)in vitroand functions as a highly efficacious experimental vaccine. Here, we characterize thehost immune response andin vivopathogenesis of HSV-1 0ΔNLS relative to its fullyvirulent parental strain in C57BL/6 mice. Additionally, we explore the role of type 1interferon (IFN-/) signaling on virulence and immunogenicity of HSV-1 0ΔNLS anduncover a probable sex bias in the induction of IFN-/in the cornea during HSV-1infection. Our data show that HSV-1 0ΔNLS lacks neurovirulence even in highly im-munocompromised mice lacking the IFN-/receptor. These studies support thetranslational viability of the HSV-1 0ΔNLS vaccine strain by demonstrating that, whileit is comparable to a virulent parental strain in terms of immunogenicity, HSV-10ΔNLS does not induce significant tissue pathology

Royer_JV_2017 (pdf)Download

A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks

A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity 

Correlates of immunologic protection requisite for an efficacious herpes simplex virus 1 (HSV-1) vaccine remain unclear with respect to viral pathogenesis and clinical disease. In the present study, mice were vaccinated with a novel avirulent, live attenuated virus (0NLS) or an adjuvanted glycoprotein D subunit (gD-2) similar to that used in several human clinical trials. Mice vaccinated with 0NLS showed superior protection against early viral replication, neuroinvasion, latency, and mortality com-pared to that of gD-2-vaccinated or naive mice following ocular challenge with a neurovirulent clinical isolate of HSV-1. More-over, 0NLS-vaccinated mice exhibited protection against ocular immunopathology and maintained corneal mechano sensoryfunction. Vaccinated mice also showed suppressed T cell activation in the draining lymph nodes following challenge. Vaccine efficacy correlated with serum neutralizing antibody titers. Humoral immunity was identified as the correlate of protection against corneal neovascularization, HSV-1 shedding, and latency through passive immunization. Overall, 0NLS affords remarkable protection against HSV-1-associated ocular sequelae by impeding viral replication, dissemination, and establishment of latency.

Royer_JV_2016 (pdf)Download

Antibodies Are Required for CompleteVaccine-Induced

Antibodies Are Required for CompleteVaccine-Induced Protection against HerpesSimplex Virus 2

Herpes simplex virus 2 (HSV-2) 0ΔNLS is a live HSV-2ICP0-mutant vaccine strain that is profoundly attenuated invivo due to its interferon-hypersensitivity. Recipients of the HSV-20ΔNLS vaccine are resistant to high-dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study,we investigated the requirements for HSV-2 0ΔNLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0ΔNLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV-2 challenge.

Halford_PLOSONE_2015b (pdf)Download

Herpes Simplex Virus 2 (HSV-2) Infected CellProteins

Herpes Simplex Virus 2 (HSV-2) Infected CellProteins Are among the Most DominantAntigens of a Live-Attenuated HSV-2 Vaccine


Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a liveHSV-2ICP0-mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE6:e17748). Inlight of these results, we sought to determine which viral proteins were the dominant anti-body-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins.



Halford_PLOSONE_2015a-1 (pdf)Download

DownloadsPan-HSV-2 IgG Antibody in Vaccinated Mice

Pan-HSV-2 IgG Antibody in Vaccinated Mice and GuineaPigs Correlates with Protection against Herpes SimplexVirus 2


We lack a correlate of immunity to herpes simplex virus 2 (HSV-2) that may be used to differentiate whether a HSV-2 vaccine elicits robust or anemic protection against genital herpes. This gap in knowledge is often attributed to a failure to measure the  correct  component  of  the  adaptive  immune  response  to  HSV-2.  However,  efforts  to  identify  a  correlate  of  immunity have focused on subunit vaccines that contain less than 3% of HSV-2’s 40,000-amino-acid proteome. We were interested to determine  if  a  correlate  of  immunity  might  be  more  readily  identified  if1.animals  were  immunized  with  apolyvalent immunogen such as a live virus and/or2.the magnitude of the vaccine-induced immune response was gauged in terms of the IgG antibody  response  to  all  of  HSV-2’s  antigens  (pan-HSV-2  IgG).  Pre-challenge  pan-HSV-2  IgG  levels  and  protection against HSV-2 were compared in mice and/or guinea pigs immunized with a gD-2 subunit vaccine, wild-type HSV-2, or oneof several attenuated HSV-2ICP02viruses (0D254, 0D810, 0DRING, or 0DNLS). These six HSV-2 immunogens elicited a wide range of pan-HSV-2 IgG levels spanning an,500-fold range. For 5 of the 6 immunogens tested, prechallenge levels of pan-HSV-2  IgG  quantitatively  correlated  with  reductions  in  HSV-2  challenge  virus  shedding  and  increased  survival  frequency following  HSV-2  challenge.  Collectively,  the  results  suggest  that  pan-HSV-2  IgG  levels  may  provide  a  simple  and  useful screening  tool  for  evaluating  the  potential  of  a  HSV-2  vaccine  candidate  to  elicit  protection  against  HSV-2  genital  herpes.

Halford_PLOSONE_2013 (pdf)Download

A Live-Attenuated HSV-2ICP02Virus Elicits 10 to 100Times

A Live-Attenuated HSV-2ICP02Virus Elicits 10 to 100Times Greater Protection against Genital Herpes than aGlycoprotein D Subunit Vaccine


Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry’s lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been on going for 20 years at a cost in excess  of$100  million.  To  date,  gD-2  vaccines  have  yielded  equivocal  protection  in  clinical  trials.Therefore,  using  a  small  animal  model,  we sought  to  determine  if  a  live-attenuated  HSV-2ICP02virus  would  elicit  better protection   against   genital   herpes   than   a   gD-2   subunit   vaccine. Mice immunized with gD-2 and a potent   adjuvant(alum+monophosphoryl  lipid A)  produced high titers of gD-2 antibody.  While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2ICP02virus, 0DNLS, survived the same HSV-2  MS  challenges.  Likewise,  0DNLS-immunized  mice  shed  an  average  125-fold  less  HSV-2  MS  challenge  virus  per  vagina relative to gD-2-immunized mice.In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed toestablish  a  detectable  infection  in  0DNLS-immunized  mice,  whereas  the  same  virus  readily  infected  naı ̈ve  and  gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if itcontained  a  live-attenuated  HSV-2  virus  rather  than  a  single  HSV-2  protein.

Halford_PLOSONE_2011 (pdf)Download

Herpes Simplex Virus 2ICP02Mutant Viruses AreAvirulent

Herpes Simplex Virus 2ICP02Mutant Viruses AreAvirulent and Immunogenic: Implications for a GenitalHerpes Vaccine


Herpes simplex virus 1 (HSV-1)ICP02mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV-1(Virol J, 2006, 3:44). If anICP02mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate  against genital herpes. The current  study  was  initiated  to  explore  this  possibility.  Several  HSV-2ICP02mutant  viruses  were  constructed  and  evaluated in term of three  parameters:i.interferon-sensitivity;ii.virulence  in  mice;andiii.capacity to elicit protective immunity against HSV-2. OneICP02mutant virus in particular, HSV-2 0DNLS, achieved anoptimal  balance  between  avirulence  and  immunogenicity.  HSV-2  0DNLS  was  interferon-sensitive  in  cultured  cells.  HSV-20DNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent hostimmune response. HSV-2 0DNLS failed to spread from sites of inoculation, and hence produced only inapparent infections.Mice  inoculated  with  HSV-2  0DNLS  consistently mounted  an  HSV-specific  IgG  antibody  response,  and  were  consistently protected  against  lethal  challenge  with  wild-type  HSV-2.  Based  otheir avirulence and  immunogenicity,  we propose that HSV-2 ICP02mutant  viruses  merit  consideration for their potential to prevent the spread of HSV-2 and genital  herpes

Halford_PLOSONE_2010 (pdf)Download

Scientific lectures by Dr. William Halford

Part 1 - An Introduction to the α-Herpesviruse and a very in-depth look into the behavior of Herpes simplex.


Part 2, Viral Countermeasures & Recurrent Herpes

Part 2 of Dr. Halford's Lecture on Herpes simplex. Also he discusses the many evasion strategies of herpes simplex and why it continues reinfect many people.


Part 3 of Dr. William Halford's lecture on herpes.

Copyright © 2016 Asking for a friend - All Rights Reserved.

Powered by Website Builder

Cookie Policy

This website uses cookies. By continuing to use this site, you accept our use of cookies.

Accept & Close

Announcement

I apologize for any mailing delays if you have purchased a book. They are working on it. 

Learn more