title: Neutralizing antibodies against adenovirus type 2 in normal and HIV-1-infected subjects: Implications for use of Ad2 vectors in vaccines.
abstract: Pre-existing neutralizing antibodies (NAbs) directed against vaccine vectors have attracted considerable research attention. Therefore, our aim was to establish a high-throughput economical neutralization assay to investigate the epidemiology of adenovirus type 2 (Ad2)-specific immunity in China and developed countries, including in a Chinese Human immunodeficiency virus (HIV)-1-infected population, and to guide the application of Ad2-vectored vaccines. We established a FluoroSpot-based anti-Ad2-virus neutralization assay using a recombinant replication-deficient Ad2 that expresses enhanced green fluorescent protein and standardized the critical parameters, including the choice of cell line, cell concentration, viral infective dose, and incubation time. The sera of 561 healthy individuals from China and developed countries and from 230 HIV-1-infected Chinese individuals were screened with this assay for Nabs against Ad2. The prevalence of anti-Ad2 NAbs was high in both China (92.2%) and developed countries (86.9%). Of the Ad2-seropositive individuals, 64.6% in China and 77.4% in developed countries had high NAb titers (> 810). The frequency of anti-Ad2 NAbs was higher in Anhui (97.5%) than in Beijing (88.7%). Their prevalence differed significantly according to age in Beijing, but not in Anhui Province, but by sex in neither province. Ad2 seroprevalence was as high among HIV-1-infected individuals (88.7%) as among healthy individuals (92.2%) in China. In conclusion, a simple, intuitive, high-throughput, economical fluorescence-based neutralization assay was developed to determine anti-Ad2 NAbs titers. Ad2 exposure was high in both healthy and HIV-1-infected populations in China, so vectors based on Ad2 may be inappropriate for human vaccines.
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Huang
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Aijing
authors.initials: A
authors.lastname: Song
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Jiajing
authors.initials: J
authors.lastname: Wu
authors.affiliation: a Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , Beijing , China.
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000257:Adenoviridae Infections / Q000276:immunology*; D000260:Adenoviruses, Human / Q000276:immunology*; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002681:China; D004337:Drug Carriers / Q000008:administration & dosage*; D016021:Epidemiologic Studies; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D015658:HIV Infections / Q000150:complications*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D016036:Seroepidemiologic Studies; D014765:Viral Vaccines / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004337:Drug Carriers; D014765:Viral Vaccines
keywords: HIV-1; adenovirus type 2; neutralizing antibody; vaccine; vector