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Commentary
Frequency of Revaccination
against Smallpox
Samuel Baron,* Jingzhi Pan,* and Joyce Poast*
*University of Texas Medical Branch, Galveston, Texas, USA
Suggested citation
for this article:
Baron S, Pan J, Poast J. Frequency of revaccination against smallpox.
Emerg Infect Dis [serial online] 2003 Nov [date cited]. Available
from: URL: http://www.cdc.gov/ncidod/EID/vol9no11/02-0820.htm
Recent suggestions to revise guidelines that recommend extending the
time for revaccination beyond 10 years may be based on insufficient and
conflicting evidence of persistence of immunity (1,2).
The evidence that cell-mediated immunity and neutralizing antibody persist
after one vaccination is conflicting (2–5). This residual
immunity is often low, and its protective activity in vivo is unclear.
Similarly, in vivo reports of durable immunity to smallpox (1)
were not sufficiently controlled, and short persistence of resistance
to dermal challenge with the antigenically related vaccinia virus has
been reported (3,6).
We confirmed the previous report (5) that the residual
antivaccinia virus titers of serum samples from singly vaccinated adults
are low (average 32) (Table). The titer of normal
commercial immunoglobulin (Ig) (Panglobulin) (11 times concentrated sera)
was 150 U/mL, which when calculated to include the 11-fold concentration,
confirms the low residual titers.
The titers of the control, unvaccinated persons, averaged 14, raising
questions about the importance and specificity of the residual antibody
in vaccinated persons. We determined that the persistent neutralizing
activity is mainly IgG antibody in serum from both single-vaccinated persons
and ordinary commercial IgG, since sequential absorption with protein
G beads and anti-IgG beads reduced the titers 80%. However, the neutralizing
activity in unvaccinated control serum may not be mainly IgG antibody
since neutralizing activity was reduced by an average of 48%, favoring
nonspecific inhibitors. Studies of these nonspecific inhibitors and possible
cross-immunizing antigens in the environment should be conducted to explain
the occurrence of neutralizing activity in serum of unvaccinated persons.
To determine whether the low residual titers in sera from single vaccinated
persons protected in vivo against a systemic infection, mice were pretreated
subcutaneously with 1 mL of either 1) serum from a single-vaccinated study
participant containing the low 10 U/mL neutralizing activity (patient
A), 2) serum from a single-vaccinated person containing the higher 43
U/mL (patient E), or 3) normal commercial Ig containing 150 U/mL and challenged
24 hours later with one LD100 vaccinia virus, strain IHD-E,
intraperitoneally. The 1 mL of serum injected into the mice is estimated
to provide its original titer in the mouse. The lowest titer serum (10
U/mL) did not protect the mice against lethal systemic infection, whereas
the highest titer serum (43 U/mL) and the commercial Ig (150 U/mL) protected
50% of the mice. Thus, the levels of residual antibody in vaccinated persons
are either not protective or only partially protective in mice. Consistent
with the reported protection by the higher levels of antibody, vaccinia
immune globulin (VIG), which contains 500 neutralizing U/mL, is effective
under some conditions (7–10). As a positive control for
protection in this animal model, 100 mg of the interferon inducer Poly
I:CLC protected 100% of the mice. Undetermined and requiring study is
whether active immunity might be protective through an anamnestic response.
The animal models of poxvirus infection have been used to evaluate immunity,
but no generally established laboratory surrogate exists for immunity
to smallpox virus itself. Persistence of effective humoral immunity after
a single vaccination and its ability to effectively protect in vivo remain
questionable.
Acknowledgments
We thank Tasnee
Chonmaitree and David Hudnall for providing serum samples.
Dr. Baron is a professor
in the Department of Microbiology and Immunology and the Department
of Internal Medicine at the University of Texas Medical Branch at Galveston.
He conducts research on the pathogenesis of virus infections and host
defenses, including interferon, immunity, smallpox, HIV, and respiratory
viruses.
References
- Cohen J. Smallpox
vaccinations: how much protection remains? Science 2001;294:985.
- Frelinger JA, Garba ML. Responses
to smallpox vaccine. N Engl J Med 2002;347:689–90.
- Moller-Larsen A, Haahr S. Humoral
and cell-mediated immune responses in humans before and after revaccination
with vaccinia virus. Infect Immun 1978;19:34–9.
- Demkowicz WE, Jr., Littaua RA, Wang J, Ennis FA. Human
cytotoxic T-cell memory: long-lived responses to vaccinia virus.
J Virol 1996;70:2627–31.
- Stienlauf S, Shoresh M, Solomon A, Lublin-Tennenbaum T, Atsmon Y,
Meirovich, et al. Kinetics
of formation of neutralizing antibodies against vaccinia virus following
re-vaccination. Vaccine 1999;17:201–4.
- Speers WC, Wesley RB, Neff JM, Goldstein J, Lourie B. Evaluation
of two kinds of smallpox vaccine: CVI-78 and calf lymph vaccine. II.
Clinical and serologic observations of response to revaccination with
calf lymph vaccine. Pediatr Res 1975;9:628–32.
- Douglas RG, Lynch; EC, Spira M. Treatment
of progressive vaccinia. Arch Intern Med 1972;129:980–3.
- Kesson AM, Ferguson J K, Rawlinson WD, Cunningham AL. Progressive
vaccinia treated with ribavirin and vaccinia immune globulin. Clin
Infect Dis 1997;25:911–4.
- Goldstein JA, Neff JM, Lane JM, Koplan JP. Smallpox
vaccination reactions, prophylaxis, and therapy of complications.
Pediatrics 1975;55:342–7.
- Feery BJ. Adverse
reactions after smallpox vaccination. Med J Aust 1977;2:180–3.
| Table.
Residual vaccinia virus neutralizing titers of serum from vaccinated
and unvaccinated persons |
|
|
Participant no.
|
Y after vaccination
|
Neutralizing titer
|
|
|
Single-vaccinated persons
|
|
|
|
A
|
47
|
10
|
|
B
|
50
|
26
|
|
C
|
45
|
27
|
|
D
|
40
|
34
|
|
E
|
40
|
43
|
|
Ordinary commercial immunoglobulin (Panglobulin)
|
|
150
|
|
Unvaccinated persons
|
|
|
|
H6
|
—a
|
<10
|
|
H9
|
—
|
<10
|
|
C2
|
—
|
<10
|
|
C4
|
—
|
<10
|
|
H1
|
—
|
10
|
|
H2
|
—
|
10
|
|
H13
|
—
|
10
|
|
C1
|
—
|
10
|
|
C3
|
—
|
10
|
|
H7
|
—
|
10
|
|
HL
|
—
|
20
|
|
H3
|
—
|
20
|
|
H4
|
—
|
20
|
|
H5
|
—
|
20
|
|
H10
|
—
|
20
|
|
H11
|
—
|
20
|
|
H12
|
—
|
20
|
|
C7
|
—
|
20
|
|
H8
|
—
|
30
|
|
| a—, Not applicable. |
|
