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Jesus Chuy

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Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir

  1. Michael T. Hensela, 
  2. Jason D. Marshalla,
  3. Michael R. Dorwartb*, 
  4. Darren S. Heekec*, 
  5. Eileen Raoc*,
  6. Padmaja Tummalad*, 
  7. Li Yue, 
  8. Gary H. Cohenf,
  9. Roselyn J. Eisenbergg and 
  10. Derek D. Sloand*
  1. aVaccine Platform Group, MedImmune, Gaithersburg, Maryland, USA
  2. bVaccine Protein Biochemistry Group, Medimmune, Mountain View, California, USA
  3. cApplied Immunology and Microbiology Group, MedImmune, Mountain View, California, USA
  4. dTranslational Biology Group, MedImmune, Mountain View, California, USA
  5. eStatistical Sciences, MedImmune, Gaithersburg, Maryland, USA
  6. fDepartment of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  7. gDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  1. Richard M. Longnecker, Editor

+Author Affiliations

  1. Northwestern University


Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo. In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses.

IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors of clinical trials. Attempts to develop a vaccine have focused primarily on glycoproteins necessary for HSV-2 entry as target antigens and to which the dominant neutralizing antibody response is directed during natural infection. Individuals with asymptomatic infection have exhibited T cell responses against specific HSV-2 antigens not observed in symptomatic individuals. We describe for the first time the immunogenicity profile in animal models of UL40, a novel HSV-2 T cell antigen that has been correlated with asymptomatic HSV-2 disease. Additionally, vaccine candidates adjuvanted by a robust formulation of the CpG oligonucleotide delivered in emulsion were superior to unadjuvanted or MPL-alum-adjuvanted formulations at eliciting a robust cell-mediated immune response and blocking the establishment of a latent viral reservoir in the guinea pig challenge model of HSV-2 infection.

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    • Nameshame
      @WilsoInAus do you really thing that above my symptoms are Herpes related? Or it may because of Herpes zoster shingles? Bcz of this my Igm is positive?
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      @WilsoInAus i requested my partner, but they are refusing from testing and saying they dint had any symptoms. Now the only way i left is to wait untill 12 weeks window period right? I am not getting what to do in this case. Any suggestion for any other tests?
    • CHT
      Hi "Jeremy"..... I agree, the topic of your HSV status does not need to be something you disclose too soon in a developing relationship..... get to know each other first....see how it's going and as it progresses, then the HSV issue will naturally need to be revealed.... it's my personal opinion though that before there is any sexual encounter you ought to disclose your HSV status.... I know some will disagree with me on this but, I think it is morally wrong not to disclose first.  This can be a make/break situation for most people but, again, I feel it is simply wrong not to give the other person the whole story since your decision not to disclose could put their health at risk.... that is simply not an option in my opinion.  Looking back to my "pre-HSV" life I most certainly would want my partner to disclose their HSV+ status before intimacy so that I could make my decision as to whether I want to take that risk or not.... 
    • Jeremy Spokein
      Thanks, CHT. I appreciate the feedback. The whole trauma of going through this has led me to figure out a lot about myself and my attachment wounds, so I'm taking courses to come out of this better. This girl really was my dream woman in so many ways, it's been the hardest heartbreak to deal with ever. I'm truly in a lot of pain, but using the pain as fuel to launch that new business and work with coaches. I also opened up to my family about HSV, so my parents and sister know now, and they were very loving and accepting of it. Since opening up about it, I feel way better around this thing. After opening up, I also found out that some mutual friends in our family have discordant couples who are married with children, so HSV hasn't stopped them from living a loving life. The thing is... all of these couples I mention did not disclose until 6-8 months into the relationship. So now I'm thinking it might be better not to disclose until I know things are very serious. I'll of course stay on the medication and use protection, but maybe this is a better route than disclosing upfront and scaring women off.
    • WilsoInAus
      Hey @Lcj987 and welcome to the website. You can be sure that isn't HSV-2, looks nothing like it. It is much more likely to be folliculitis or inflamed fordyce spots.
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