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Journal of Virology, November 1999, p. 9609-9613, Vol. 73, No. 11
Department of Gynecology, Centre Hospitalier
Universitaire Vaudois, CH-1011 Lausanne,
Switzerland,1 and Laboratory of Cellular
Oncology, National Cancer Institute, Bethesda, Maryland
20892-40402
Received 12 May 1999/Accepted 23 July 1999
We have recently shown that nasal immunization of anesthetized mice
with human papillomavirus type 16 (HPV16) virus-like particles (VLPs)
is highly effective at inducing both neutralizing immunoglobulin A
(IgA) and IgG in genital secretions, while parenteral immunization induced only neutralizing IgG. Our data also demonstrated that both
isotypes are similarly neutralizing according to an in vitro pseudotyped neutralization assay. However, it is known that various amounts of IgA and IgG are produced in genital secretions along the
estrous cycle. Therefore, we have investigated how this variation influences the amount of HPV16 neutralizing antibodies induced after
immunization with VLPs. We have compared parenteral and nasal protocols
of vaccination with daily samplings of genital secretions of mice.
Enzyme-linked immunosorbent assay analysis showed that total IgA and
IgG inversely varied along the estrous cycle, with the largest amounts
of IgA in proestrus-estrus and the largest amount of IgG in diestrus.
This resulted in HPV16 neutralizing titers of IgG only being achieved
during diestrus upon parenteral immunization. In contrast, nasal
vaccination induced neutralizing titers of IgA plus IgG throughout the
estrous cycle, as confirmed by in vitro pseudotyped neutralization
assays. Our data suggest that mucosal immunization might be more
efficient than parenteral immunization at inducing continuous
protection of the female genital tract.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Mucosal but Not Parenteral Immunization with
Purified Human Papillomavirus Type 16 Virus-Like Particles Induces
Neutralizing Titers of Antibodies throughout the Estrous Cycle
of Mice
*
Corresponding author. Mailing address:
Département de Gynécologie, c/o Institut de Microbiologie,
Bugnon 44, 1011 Lausanne, Switzerland. Phone: 21/314 40 81. Fax: 21/314
40 95. E-mail: DNARDELL{at}hola.hospvd.ch.
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