Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial

Greenberg, Richard N.; Kennedy, Jennifer; Clanton, David J.; Plummer, Elizabeth A.; Hague, Lynda; Cruz, John; Ennis, Francis A.; Blackwelder, William C.; Hopkins, Robert J.

doi:10.1016/s0140-6736(05)17827-1

Cited by 42 publications

(46 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hsieh et al also found that previous vaccination status did not affect the cell-mediated immune response 1 month after smallpox vaccination (5), and Greenberg et al obtained the same result using a new cellcultured smallpox vaccine (4). Our finding on the lack of effect of previous vaccination status is thus in line with these previous studies (4,5,6). In an earlier report (8), we also showed that a certain extent of vaccine dilution, and preexisting immunity to vaccinia virus, did not affect the immunologic set points of the humoral immune response 1 month after smallpox vaccination.…”

supporting

confidence: 93%

“…However, assessment of the effectiveness of the attenuated forms of smallpox vaccines (i.e., modified vaccinia Ankara strain, New York City Board of Health strain [NYCBH], or LC16m8) and the next generation of smallpox vaccines requires a broader understanding of the immune response to vaccinia virus (4). However, there are limited and sometimes conflicting data on the dependence of human cell-mediated immune responses to smallpox vaccination on vaccine dilutions (3,5,9) and previous vaccinia vaccination status (4,5,6). We have therefore evaluated whether vaccine dilutions or previous vaccination status affect the induction of cell-mediated immune responses to smallpox vaccination.…”

mentioning

confidence: 99%

“…In addition, we used PBMC stimulated with vaccinia virus for a short time (1 h) as in a previous study (1), while longer stimulation times (more than 18 h) were used by others (9,10). Differences in the virus strain used for vaccination could also affect the result as mentioned above; the Lister strain (the present study) versus the NYCBH strain (2,3,4,6,9,10,11). In addition, the IFN-␥-producing spots in the ELISPOT assay do not measure CD8 virus."…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cell-Mediated Immune Responses to Smallpox Vaccination

Kim

Yeo

Cho

et al. 2006

Clin Vaccine Immunol

View full text Add to dashboard Cite

We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus vaccination status had no significant effect on cell-mediated immune responses (i.e., the immediate vaccinia virus-specific gamma interferonproducing T-cell response measured by enzyme-linked immunospot assay) 1 month after smallpox vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).The evaluation of successful vaccination with vaccinia virus is based on visual confirmation of a dermal response (10). However, assessment of the effectiveness of the attenuated forms of smallpox vaccines (i.e., modified vaccinia Ankara strain, New York City Board of Health strain [NYCBH], or LC16m8) and the next generation of smallpox vaccines requires a broader understanding of the immune response to vaccinia virus (4). However, there are limited and sometimes conflicting data on the dependence of human cell-mediated immune responses to smallpox vaccination on vaccine dilutions (3, 5, 9) and previous vaccinia vaccination status (4,5,6). We have therefore evaluated whether vaccine dilutions or previous vaccination status affect the induction of cell-mediated immune responses to smallpox vaccination. Cell-mediated immune responses to smallpox vaccination were assessed as the immediate vaccinia virus-specific gamma interferon (IFN-␥)-producing T-cell response by enzyme-linked immunospot (ELISPOT) assays. The assay was performed as described previously (1, 7). Briefly, approximately 60 ml of venous blood was obtained from each volunteer in this trial just before vaccination (day 0) and 30 days after vaccination. Within 6 h of collection, peripheral blood mononuclear cells (PBMC) were isolated by using Ficoll-Hypaque density gradients. The PBMC were then resuspended at a concentration of 10 7 cells/ml in RPMI 1640-20% fetal bovine serum-10% dimethyl sulfoxide and were cryopreserved. The cryopreserved PBMC were thawed and washed once with RPMI 1640 supplemented with 10% fetal bovine serum and 50 U of Benzonase (Sigma-Aldrich)/ml. Cells were again washed and then resuspended with RPMI 1640 supplemented with 10% fetal bovine serum at a concentration of 5 ϫ 10 6 cells/ml. The prepared PBMC were infected for 1 h with the live vaccinia virus (fresh vaccinia virus obtained from lyophilized LancyVaxina vaccine) at a multiplicity of infection of 1. Cells were washed and added to 96-well ELISPOT plates (BD Biosciences Pharmingen) coated with anti-human IFN-␥ antibody (BD ELISPOT human IFN-␥ kit). Negative controls were uninfected cells with medium alone. Positive controls were uninfected PBMC stimulated with purified phytohemagglutinin (Sigma-Aldrich). Cells were cultured in duplicate wells at 5 ϫ 10 5 cells/well at 37°C for 18 h. Spots were counted by use of an automated microscope (Carl Zeiss MicroImaging, Inc., Germany) after the background value, obtained by using unstimulated cells, was subtracted. A postvaccination response for cell-mediated immunity was defined as positive if the vaccinia virus-specific IFN-␥-producing T-cell response by ELISPOT assays increased...

show abstract

supporting

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cell-Mediated Immune Responses to Smallpox Vaccination

Kim

Yeo

Cho

et al. 2006

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…Several studies have identified proteins important for the elicitation of neutralizing antibodies (13,21). A recent trial with dilutions of the licensed smallpox vaccine Dryvax in human volunteers confirmed that pustule formation strongly correlated with the development of both the specific antibodies and with the induction of cytotoxic T lymphocytes (CTL) and elevated IFN-␥ cell responses (14). Neither these studies nor our own work have fully characterized the CTL responses, but an assessment of virus-specific T cells expressing IFN-␥ in mice vaccinated with VV/NE clearly indicated that NE nasal vaccination induces a potent activation of VV-specific MHC class I-restricted CD8 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine

Bielinska

Чепурнов

Landers

et al. 2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

“…This enhanced response to tail scarification could be the result of the proximity of the inoculating virus to the important first messengers of the immune response, ostensibly Langerhans cells, or it may reflect the propensity of LC16m8 to grow on skin, since it was selected for growth at reduced temperatures (13). A reduced immune response was also observed for clinical trials in which vaccinia virus was administered by alternatives to the percutaneous route (12).…”

Section: Discussionmentioning

confidence: 91%

Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model

Meseda

Mayer

Kumar

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

The immune response elicited by LC16m8, a candidate smallpox vaccine that was developed in Japan by cold selection during serial passage of the Lister vaccine virus in primary rabbit kidney cells, was compared to Dryvax in a mouse model. LC16m8 carries a mutation resulting in the truncation of the B5 protein, an important neutralizing target of the extracellular envelope form of vaccinia virus (EV). LC16m8 elicited a broad-spectrum immunoglobulin G (IgG) response that neutralized both EV and the intracellular mature form of vaccinia virus and provoked cell-mediated immune responses, including the activation of CD4 ؉ and CD8 The last naturally occurring case of smallpox was reported in 1977. Following the successful containment of a laboratoryacquired case in Birmingham, England, in 1978, smallpox was officially declared eradicated by the World Health Organization in 1980, after the disease had claimed millions of human lives across the globe during a pandemic that lasted several millennia. Despite the eradication of smallpox, the potential for a reemergence of smallpox and a prevailing threat of clinical infections by other poxviruses associated with smallpoxlike symptoms in humans make a sustained supply of smallpox vaccines imperative. For example, outbreaks of zoonotic monkeypox virus infection of humans have been reported in different parts of the world in the past four decades (4, 17), including a 2003 outbreak in the United States (5, 31).Adverse events associated with traditional smallpox vaccines necessitated the quest for new vaccines with less reactogenicity. Two attenuated smallpox vaccines, modified vaccinia virus Ankara (MVA) (25) and a Lister virus derivative (LC16m8), underwent considerable development near the end of the smallpox eradication campaign. LC16m8 was developed as an attenuated smallpox vaccine in Japan in the early 1970s by about 45 serial passages and cold selection of the Lister/Elstree vaccine virus in primary rabbit kidney cells (13). Unlike MVA, LC16m8 does not carry large deletions of gene blocks in its genome and can replicate productively in mammalian cells. Similar to its parent virus strain (Lister/Elstree), for instance, inoculation of LC16m8 by scarification on the skin surface results in a "take" that manifests as a pock lesion that is characteristic of replication-competent smallpox vaccines. In a number of animal models (mice, rabbits, and monkeys), vaccination with LC16m8 conferred protection against lethal poxvirus challenge (7, 32; reviewed in reference 20). LC16m8 was used as a smallpox vaccine in Japanese children at the end of the smallpox eradication campaign in the 1970s, but its efficacy against smallpox is unknown, since smallpox was no longer endemic at the time of its use. A major genetic difference between LC16m8 and the parent Lister vaccine strain used in the campaign to eradicate smallpox has been mapped to a single-base-pair deletion within the open reading frame that encodes the vaccinia virus B5 protein (28,38). This mutation creates a stop codon in B...

show abstract

Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial

Cited by 42 publications

References 13 publications

Cell-Mediated Immune Responses to Smallpox Vaccination

Cell-Mediated Immune Responses to Smallpox Vaccination

A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine

Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model

Contact Info

Product

Resources

About