Smallpox vaccine dogma challenged

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Nature Reviews Immunology 3, 779 (2003); doi:10.1038/nri1209

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[609K] VACCINES

Smallpox vaccine dogma challenged

Sheilagh son Associate Editor, Nature Reviews Microbiology

The widely held belief that the smallpox vaccine only provides protection

against smallpox for 3–5 years is untrue, according to a new study in Nature

Medicine.

The vaccine, which was routinely administered in the United States until

1972, comprises live vaccinia virus, an orthopoxvirus that is closely related to

variola, the causative agent of smallpox. In the largest study of its kind so

far, a team of researchers at Oregon Health and Science University, United

States analysed the antiviral immune response in 306 volunteers who had been

vaccinated against smallpox at least once in their lifetime. The timing of the

vaccinations varied from between one month before testing to 75 years before

testing.

The cell-mediated immune response was quantified using an ex vivo assay that

detects the production of interferon-<A

HREF= " http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3458 " > (IFN-</A>) and

tumour-necrosis factor <A

HREF= " http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7124 " >(TNF)</A>

by peripheral-blood mononuclear cells following direct challenge with

vaccinia. The smallpox vaccine stimulates a strong virus-specific CD4+ and CD8+

T-cell

response, which declines slowly with an average half-life of 8–15 years.

Hammarlund et al. then used a vaccinia-specific enzyme-linked immunosorbent

assay and a neutralization assay to detect vaccinia-specific antibodies. In

contrast to the cell-mediated response, the humoral immune response was shown to

remain steady for as long as 75 years and could therefore have a greater role

in smallpox immunity than was previously thought.

It has long been maintained that repeated vaccination against smallpox is

required for maximal protection against the disease. However, analysis of the

immune response of volunteers who had been immunized more than once revealed

that

although repeated vaccination resulted in a short-term boost in immune

responses, it did not markedly increase the levels of long-term cell-mediated or

humoral immunity.

These results indicate that the prevailing immunity to smallpox in the

general population in the United States is greater than was previously thought.

More

than 90% of the participants in the study showed measurable cell-mediated or

humoral immunity to smallpox. Given that more than 90% of Americans over the

age of 35 — some 140–150 million individuals — have been vaccinated

against

smallpox, this could provide at least some degree of herd immunity in the event

of an outbreak.

References and links

ORIGINAL RESEARCH PAPER

Hammarlund, E. et al. Duration of antiviral immunity after smallpox

vaccination. Nature Med. 9~1131~1137(2003) | <A

HREF= " http://www.nature.com/doifinder/10.1038%2Fnm917 " >Article</A> | <A

HREF= " http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg & cmd=Retrieve & db=\

PubMed & list_uids=12925846 & dopt=Abstract " >PubMed</A> | <A

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g & version=1.0 & coi=1:CAS:528:DC%2BD3sXmvVWnsrk%3D & pissn=1474-1733 & pyear=2003 & md5=\

2819af7c2446fea2815f543c58d49113 " >ChemPort</A> |

FURTHER READING

, G. L. & McFadden, G. Smallpox: anything to declare? Nature Rev.

Immunol. 2, 521-527 (2002). | <A

HREF= " http://www.nature.com/doifinder/10.1038%2Fnri845 " >Article</A> | <A

HREF= " http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg & cmd=Retrieve & db=\

PubMed & list_uids=12094226 & dopt=Abstract " >PubMed</A> | <A

HREF= " http://links.isiglobalnet2.com/gateway/Gateway.cgi? & GWVersion=2 & SrcAuth=Na\

ture & SrcApp=Nature & DestLinkType=FullRecord & KeyUT=000180438800016 & DestApp=WOS_CPL\

" >ISI</A> | <A

HREF= " http://chemport.cas.org/cgi-bin/sdcgi?APP=ftslink & action=reflink & origin=np\

g & version=1.0 & coi=1:CAS:528:DC%2BD38XkvFKks78%3D & pissn=1474-1733 & pyear=2003 & md5=\

21fa20be2213ee4880f40ee3aacfd217 " >ChemPort</A> |

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