To assess the potential for cross-protection among genital human papillomavirus (HPV) types in virus-like particle (VLP)-based vaccinations, inhibition of HPV VLP-mediated hemagglutination by rabbit antisera raised against HPV type 6b (HPV-6b), HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45 was analyzed. Only highly homologous types (HPV-6b and HPV-11, and HPV-18 and HPV-45) exhibited detectable serological cross-reaction for the class of antibodies that inhibit virion-to-cell surface binding. However, analysis of neutralizing monoclonal antibodies to several animal and human papillomaviruses indicated that over half of these antibodies do not prevent cell surface binding, but these latter antibodies do not appear to be more cross-reactive in enzyme-linked immunosorbent assays than those that mediate inhibition of hemagglutination. The data strongly suggest that while there may be limited cross-protection between highly (>85% L1 amino acid identity) homologous types, protection by HPV VLP-based vaccines will be predominantly type specific.
Journal Article A Virus-Like Particle Enzyme-Linked Immunosorbent Assay Detects Serum Antibodies in a Majority of Women Infected With Human Papillomavirus Type 16 Get access Reinhard Kirnbauer, Reinhard Kirnbauer Search for other works by this author on: Oxford Academic PubMed Google Scholar Nancy L. Hubbert, Nancy L. Hubbert Search for other works by this author on: Oxford Academic PubMed Google Scholar Cosette M. Wheeler, Cosette M. Wheeler Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas M. Becker, Thomas M. Becker Search for other works by this author on: Oxford Academic PubMed Google Scholar Douglas R. Lowy, Douglas R. Lowy Search for other works by this author on: Oxford Academic PubMed Google Scholar John T. Schiller John T. Schiller Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 7, 6 April 1994, Pages 494–499, https://doi.org/10.1093/jnci/86.7.494 Published: 06 April 1994 Article history Received: 19 August 1993 Revision received: 30 November 1993 Accepted: 05 January 1994 Published: 06 April 1994
SUMMARY Slide agglutination and mercaptoethanol tube agglutination tests for canine brucellosis were performed on 158 dogs. Clinical status was compared with the serologic test results. Sera were from 56 clinically normal dogs, 63 dogs with reproductive disorders, and 39 dogs with various nonreproductive disorders that could be associated with canine brucellosis. Ten of 21 (48%) aborting bitches and 2 of 9 (22%) bitches with other reproductive disorders were seropositive for brucellosis. Enlarged testicles, orchitis, and epididymitis were the main clinical disorders associated with positive (33%) or suspect (20%) serologic reactions in 15 male dogs. In 13 dogs of both sexes, diskospondylitis and osteomyelitis were the most common nonreproductive disorders associated with seropositive status for canine brucellosis (46%). Of 138 stray dogs, 17 were seropositive for canine brucellosis. Treatment of seropositive animals with antibiotics gave variable results. Of the 296 serum samples tested, 43 (14.5%) gave a positive reaction by the slide agglutination test but were negative by the mercaptoethanol tube agglutination test. Correlation was not found between serologic results and sex or breed.
Seroreactivity to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) in men attending clinics for sexually transmitted diseases (STDs) in Denmark (n = 219) and Greenland (n = 88) was compared with seroreactivity in women attending the same clinics and was furthermore related to epidemiologic variables and concurrent HPV DNA detection. Risk factors for male seropositivity in Denmark were lifetime number of sex partners, a history of STDs, and sexual preference and in Greenland were ever having had syphilis and years at school. Although men reported significantly more sex partners, the mean seroreactivity was significantly lower in men than in women: 0.50 and 0.75, respectively, in Denmark and 0.53 and 0.86 in Greenland (P = .0001). Male seropositivity was not correlated with concurrent HPV DNA detection, but only 15 Danish and 6 Greenlandic men had HPV-16 DNA. Presence of HPV-16 VLP antibodies appears to be a biomarker for exposure to genital HPVs in men but is less sensitive than in women.
Virus-like particles (VLPs) composed of L1 derived from bovine papillomavirus type 1 (BPV-1), several human papillomavirus types, or cottontail rabbit papillomavirus (CRPV) agglutinated mouse but not human or rat erythrocytes. Treatment of mouse erythrocytes with trypsin prevented hemagglutination (HA) by BPV-1. Sera from rabbits immunized with native CRPV VLPs, which protect against experimental CRPV infection, exhibited high titers of antibodies that inhibited CRPV VLP HA activity, while sera from rabbits immunized with denatured CRPV VLPs or native BPV VLPs, which do not protect against CRPV infection, were not inhibitory. Testing for HA inhibition is a rapid and simple method for examining the serological relatedness of papillomaviruses and measuring protective antibody titers after VLP vaccination.
Sexually transmitted genital human papillomavirus (HPV) infection, most often HPV 16, is considered the major etiologic determinant of cervical cancer. However, some studies have found relatively low prevalences of genital tract HPV DNA in some geographical areas, such as Greenland, that have high rates of cervical cancer. We sought to evaluate HPV 16 infection in high-risk cohorts using a serologic assay that assesses prior exposure as well as current infection and to compare the results with those obtained using a sensitive PCR-based HPV DNA assay. An ELISA based on HPV 16 virus-like particles was used to detect IgG serum antibodies in women attending sexually transmitted disease (STD) clinics in Nuuk, Greenland and Copenhagen, Denmark. Using a preassigned cut-off, 56% of Greenlandic and 41% of Danish women were seropositive (p = 0.02). In Greenlandic women, there was a non-significant increase in seropositivity with age, and odds ratios for seropositivity were similar for women with more than 5 lifetime sex partners. Seropositivity in the Danish women, however, increased linearly with increases in these 2 factors, which are likely correlates of lifetime exposure to genital HPVs. In contrast, any genital HPV DNA (HPV16 specifically) was detected in 24% and 36% of Greenlandic and Danish women, respectively and was most frequently detected in women below 20. The finding that HPV DNA prevalences, unlike seroprevalences, tended to decrease with increased lifetime risk of infection, provides an explanation for the lack of correlation between HPV DNA prevalences and cervical cancer risk in previous studies of high-risk populations.
It is not known whether DNA sequence variants of human papillomavirus type 16 (HPV-16) are distinct serotypes. To examine this question, the reactivities of women's sera from Zaire (n = 97) and Denmark (n = 123) were compared in IgG-specific ELISAs based on virus-like particles (VLPs) composed of the L1 major capsid protein derived from an HPV-16 variant common in central Africa (Z-1194) or one common in northern Europe (114K). These L1s differ in seven amino acids. There was a strong correlation between reactivity in the two assays for both sets of sera (correlation coefficients, 0.73 and 0.85 for Zairian and Danish sera, respectively). In only 1 serum was there evidence for a specific reaction to one but not the other VLP variant. The results support the conclusion that the virions of strains Z-1194 and 114K are serologically cross-reactive.
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