A. Buchan

The effect of lithium chloride on the replication of herpes simplex virus.

Lithium chloride inhibited the replication of type 1 and type 2Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenza virus.

HERPESVIRAL THYMIDINE KINASES : LAXITY AND RESISTANCE BY DESIGN

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The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; Report of a prospective double blind placebo controlled trial

Abstract A randomised, placebo-controlled, multi-centre trial of intracellular subunit herpes simplex virus (HSV) type 1 vaccine NFU.Ac.HSV-1(S–)MRC (Skinner vaccine) was conducted at three medical centres in the United States. Subjects with documented herpes genitalis of at least 1-year duration and a history of six or more genital HSV recurrences in the 12 months prior to study entry were randomised to receive vaccine or placebo at 0, 1 and 2 months. Vaccination induced significant neutralising, enzyme-linked immunosorbent assay and lymphocyte transformation response to HSV-1 antigen. The frequency of recurrences was reduced in the vaccinated female patients at both 3 and 6 months following vaccination with an overall reduction in patients of both sexes which did not reach statistical significance. Recurrence severity was reduced as measured by decreased number of lesions and associated symptoms per recurrence (P = 0.04). The data suggest that clinical manifestations of latent HSV genital infection may be modified by therapeutic immunisation.

Report of twelve years experience in open study of Skinner herpes simplex vaccine towards prevention of herpes genitalis

Three hundred and forty-seven subjects at risk for herpes genitalis were vaccinated with Skinner vaccine, NFUAc.HSV1.(S−MRC 5), and were followed for an average duration of 2 years representing a total consortship of 664.4 years. Based on survey information obtained during this consortship, there were estimated to be 3076 recurrences which summated to 3.5 years total duration of disease and comprised at least 6794 lesions; there were an estimated 51997 episodes of intercourse including at least 241 episodes of unprotected intercourse in the presence of herpetic lesions. The rate of contraction of herpes genitalis was 6 of 54 consorts (11.1%) who received one vaccination and 7 of 293 (2.4%) who received two, three of four vaccinations. There was no evidence of physical or psychological side effects from vaccination.

The Immunological Relationship between Canine Herpesvirus and Four Other Herpesviruses

Canine herpesvirus (CHV) was compared with four other herpesviruses by several serological techniques. Cross-neutralization was demonstrated between CHV and herpes simplex virus types 1 and 2 and pseudorabies virus. Non-neutralizing cross-reactions were found with these viruses and also with equine abortion virus and bovine mammillitis virus. The data suggest that CHV is immunologically more closely related to herpes simplex virus than to the other viruses used in this study.

Follow-up report on 50 subjects vaccinated against herpes genitalis with Skinner vaccine.

Fifty subjects at risk of herpes genitalis received 109 immunizations with Skinner herpes vaccine and were assessed after a follow-up period of 4–48 months, respresenting a total follow-up period of 694 patient months. There was no evidence of contraction of herpes genitalis in 49 subjects. The risk of virus transmission and rate of contraction of disease was quantified by construction of two functions, namely a unit of exposure risk calculated per year (UYE) and standard contraction rate (SCR); in this study the SCR was 0.02. There was no evidence of significant side-effects from vaccination. Administration of Alhydrogel adjuvant with vaccine induced temporary granuloma formation in most subjects but was only detectable beyond 1 year of follow-up in one subject, in whom a painless swelling of 0.2 cm was detected 3 years after vaccination. There was no evidence of immunological reactivity to host cell or calf serum antigens in any of the subjects vaccinated.

The preparation, efficacy and safety of ‘antigenoid’ vaccine NFU1 (S−L+) MRC toward prevention ofHerpes simplex virus infections in human subjects

Vaccine NFU1 (S−L+) MRC was prepared by high multiplicity infection of serum-deprived human embryonic lung (MRC 5) cells with type 1Herpes simplex virus. The preparative process removed inoculum virus particles and virus DNA while virus particle and DNA synthesis was inhibited by the presence of lithium chloride in the cell culture medium. The vaccine stimulated neutralising antibody in vaccinated mice and provided long-term protection against intra-vaginal challenge with type 2 herpes virus. The safety of the vaccine was confirmed by inoculation into newborn mice and cell lines of human, mammalian, and rodent origin. There was no evidence of cell transformation in vitro or of oncogenicity or teratogenicity in rodent species. It is intended to investigate the efficiency of this vaccine in human subjects.

Growth of herpes simplex type 1 on skin explants of atopic eczema.

In a novel approach to looking at why some children with atopic eczema are susceptible to cutaneous herpes simplex virus (HSV) infections, this study evaluates the hypothesis that HSV replicates more easily on eczematous than normal skin. Growth of HSV on eczematous skin explants was compared wild growth on explants from three control groups (psoriasis, Dariers disease and normal skin) over a 2‐day period. Growth of HSV was significantly less on normal skin than in atopic eczema, psoriasis and Dariers disease. Virus replicated more quickly, and grew to higher titre within 24h, in eczematous and psoriatic explants than in normal skin. A defect in skin barrier function and host defence factors including local cytokine secretion are discussed as possible mechanisms in causing the increased susceptibility of children with atopic eczema to HSV infection.

An outbreak of herpes rugbiorum managed by vaccination of players and sociosexual contacts

An outbreak of herpes rugbiorum involved nine players including the scrum half and the full back. The infection was characterized by significant constitutional upset with decreased levels of general fitness and match performance for 1-4 months following the outbreak; one player had herpetic lesions on his right eyelid and corneum. Every infected player, 15 non-infected players and five sociosexual contacts received two vaccinations with intracellular subunit vaccine NFU. Ac. HSV-1 (S-MRC5). None of the players or contacts developed cutaneous herpetic recurrence during a follow-up period of 3 years; the player with ocular disease had one recurrence at 30 months following the original episode. These findings encourage consideration of prophylactic or post-exposure vaccination of participants in rugby or other contact sports with this or other appropriate herpes simplex vaccine.

Role of bovine mammillitis virus towards preparation of an alternative vaccine against herpes simplex virus infections of human subjects

Bovine mammillitis virus (BMV) cross-reacted in neutralization and radioimmune assay with herpes simplex virus (HSV) and pre-immunization with BMV protected against challenge by type 2 HSV. There was no evidence to suggest a pathogenic role for BMV as adjudged by a literature search or field enquiry and BMV specific antibody was not detected in 21 human sera or in four sera from personnel engaged in research with BMV; in addition there was no replication or antigen synthesis by BMV in explants of human tissue or cell lines of human origin. It is proposed that BMV might provide an alternative vaccine against HSV infections of human subjects.