Varicella immunity and vaccination

Varicella-zoster virus (VZV) is an air-borne, extremely contagious herpesvirus. It causes chickenpox, which usually is a benign illness in childhood. Adults, pregnant women and immunocompromised patients often get a severe disease with complications. After infection the virus stays latent in sensory ganglia. It can be reactivated and cause shingles if the cellmediated immunity (CMI) deteriorates. In the western world more than 90% of adults have had chickenpox. VZV vaccines have been introduced in many countries. They have been included in the childhood vaccination programme in e.g. the USA and Germany but not in Sweden due to lack of knowledge on many aspects of long-term effects.

More detailed information on the nature of the VZV-specific immune response is needed. To provide sufficient and reliable information the studies must be performed at a large scale. Such studies have been difficult since the methods for determination of antibody mediated immunity to VZV are not well standardised and the conventional lymphoproliferation assays for CMI are labour intensive.

We therefore developed a Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA) for the detection of CMI against VZV. The results were more reproducible than with the conventional method. The sensitivity and specificity in relation to the VZV serostatus increased with immunophenotyping by cellsurface staining of the proliferating cells. FASCIA is easy to handle, can be performed at a large scale and is suitable for large scale studies on specific CMI.

Serology and FASCIA with immunophenotyping were used to compare the VZV-specific CMI response before and after immunization against VZV in VZV seronegative, adult persons and in controls with past chickenpox. One year after vaccination the humoral and the CMI responses were lower in the vaccinees than in persons with past infection. In a study to determine the feasibility of co-administration of a VZV vaccine and the measles, mumps, rubella (MMR) vaccine booster at 12 years of age, 5/17 VZV seronegative pupils did not seroconvert after one VZV vaccine. After a second dose, 3/5 that could be examined seroconverted. VZV CMI was measurable in one of them before the second dose, and in 3/3 after vaccination. The VZV vaccine did not affect the MMR-response, but the age group should be recommended 2 doses of VZV vaccine.

In the study, the seroprevalence for VZV was calculated to be 97% among the 12 years-old, which was higher than expected. We therefore evaluated if there has been a change in seroprevalence to VZV during the past 30 years, since the changes in social conditions and life-style in Sweden may have affected the spread of the viruses. The seroprevalence for the air-borne VZV had increased dramatically from 50% to 98%, and we suggest that it may be due to a change in child care pattern. The seroprevalence for HSV and EBV that infect by close contact had not changed dramatically, but there seemed to have been an unexplainable increase in the CMV sero prevalence.

List of scientific papers

I. Svahn A, Linde A, Thorstensson R, Karlén K, Andersson L, Gaines H (2003). Development and evaluation of a flow-cytometric assay of specific cell-mediated immune response in activated whole blood for the detection of cell-mediated immunity against varicella-zoster virus. J Immunol Methods. 277(1-2): 17-25
https://pubmed.ncbi.nlm.nih.gov/12799036

II. Parment PA, Svahn A, Rudén U, Bråkenhielm G, Storsaeter J, Akesson L, Linde A (2003). Immunogenicity and reactogenicity of a single dose of live attenuated varicella vaccine and a booster dose of measles-mumps-rubella vaccine given concomitantly at 12 years of age. Scand J Infect Dis. 35(10): 736-42
https://pubmed.ncbi.nlm.nih.gov/14606613

III. Svahn A, Berggren J, Parke A, Storsaeter J, Thorstensson R, Linde A (2006). Changes in seroprevalence to four herpesviruses over 30 years in Swedish children aged 9-12 years. J Clin Virol. 37(2): 118-23. Epub 2006 Sep 12
https://pubmed.ncbi.nlm.nih.gov/16971177

IV. Svahn A, Linde A, Andersson L, Pauksens K, Dahl H, Gaines H (2008). Humoral and cell-mediated varicella-zoster virus response in vaccinated and naturally infected adults in Sweden. [Submitted]