Evaluation of antibodies induced by an HPV vaccine to cross-neutralize pseudovirions of vaccine-related HPV types

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15008-15008 ◽  
Author(s):  
J. T. Bryan ◽  
J. F. Smith ◽  
W. Ruiz ◽  
M. K. Brownlow ◽  
M. J. Brown ◽  
...  
Keyword(s):  
Hpv Vaccine ◽  
Neutralizing Antibodies ◽  
Neutralization Titer ◽  
Indirect Measure ◽  
Virus Like Particle ◽  
Vaccine Type ◽  
Antibody Titers ◽  
Hpv Types ◽  
L1 And L2

15008 Background: Human papillomavirus (HPV) is the causative agent of cervical cancer. The HPV types 6, 11, 16 and 18 quadrivalent L1 virus-like particle (VLP) vaccine has been shown to be highly efficacious in preventing HPV vaccine type-related disease. The HPV A7 species contains types 18, 45 and 59. The A9 species include types 16, 31, 33, 35, 52 and 58. The potential of the vaccine induced antibodies to cross-neutralize infection of pseudovirions (PsV) of HPV types within the A9 and A7 species was evaluated. Methods: Sera from quadrivalent, monovalent HPV 16, or monovalent HPV 18 vaccinees were evaluated. Sera were tested in a multiplexed competitive Luminex Immunoassay (cLIA) against vaccine types to demonstrate HPV type-specific seroconversion. A9 and A7 VLP type cross-reactive binding ability was assessed by a total IgG LIA. HPV L1 and L2 PsV containing secreted alkaline-phosphatase (SEAP) sequences were constructed using native HPV sequences for 16 and 31 and with mammalian codon-optimized sequences for 18 and 45. Demonstrated expression of SEAP was used as an indirect measure of PsV infection of 293TT cells. Results: All subjects seroconverted to high titers against the vaccine HPV types. Cross-reactive antibodies were generated. Quadrivalent vaccinee sera bound to HPV 31, 45, 52 and 58 VLPs. These total IgG titers were 1.5–2 logs lower than the titers to the vaccine types. PsV types 18 and 45 were neutralized using the 18 monovalent and the quadrivalent sera. At month 7, the PsV 18 neutralization titer was ∼1–1.5 logs less than that required for PsV 45 cross-neutralization. Neutralization studies using PsV of the A9 species are in progress. Conclusions: High titers of anti-HPV antibodies are elicited by vaccination with HPV VLP vaccines. These antibodies can prevent in vitro PsV infection of vaccine-HPV types. Cross-reactive, cross-neutralizing antibodies are generated, however at reduced titers compared to the vaccine-specific types. Antibody titers required for cross-protection against non-vaccine types are not known. [Table: see text]

scholarly journals Induction of neutralizing antibodies by human papillomavirus vaccine generated in mammalian cells

2019 ◽  
Vol 2 (2) ◽  
pp. 45-53
Author(s):  
Xilin Wu ◽  
Xiaohua Ma ◽  
Yanlei Li ◽  
Yue Xu ◽  
Nan Zheng ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Hpv Vaccine ◽  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Potential Candidate ◽  
Human Papillomavirus Vaccine ◽  
Hpv Vaccines ◽  
Virus Like Particle ◽  
Size And Morphology ◽  
L1 And L2

ABSTRACT Background Cervical cancer caused by human papillomavirus (HPV) infections is one of the most common cancers affecting women worldwide. Current preventative HPV vaccines on the market are composed of HPV L1 protein produced either in the yeast such as Gardasil or in the insect cells such as Cervarix. The duration of efficacy and cross-protection remain highly desirable for the improvement of current prophylactic HPV vaccine. Given that HPV carries out infection and replicates in mammalian cells, L2 protein, which is not included in the current licensed vaccines, is included in the third generation of HPV vaccine in pursuing of providing broader prevention. We hypothesize that a virus-like particle (VLP) consisting of HPV L1 plus L2 proteins generated in mammalian cells will present conformations more closely to native HPV, thus it will provide more durable and broader efficacy of prevention. Methods We took advantage of 293TT cells to produce VLP containing L1 and L2 proteins of HPV16 and HPV18, respectively. Results VLP particles of uniformed size and morphology were observed, and potent and broadly neutralizing antibodies were induced in mice and rabbits. In addition, compared to bivalent HPV vaccine of Cervarix, our HPV L1-L2 VLPs elicited higher titer of anti-sera, and the anti-sera also presented comparable neutralization potency against HPV16 and HPV18 infections even a much less potent adjuvant was used in our case. Conclusion Our VLPs were capable of eliciting stronger and more broadly neutralizing activities against various HPV subtypes and were potential candidate HPV vaccines.

scholarly journals Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Rashi Yadav ◽  
Lukai Zhai ◽  
Ebenezer Tumban
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Hpv Vaccine ◽  
Genital Warts ◽  
Human Papillomaviruses ◽  
Target Antigen ◽  
Sexually Transmitted ◽  
Virus Like Particle ◽  
Protective Antibodies ◽  
Hpv Types

Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further.

scholarly journals Improved Efficiency of a Salmonella-Based Vaccine against Human Papillomavirus Type 16 Virus-Like Particles Achieved by Using a Codon-Optimized Version of L1

2004 ◽  
Vol 78 (23) ◽  
pp. 12901-12909 ◽  
Author(s):  
David Baud ◽  
Françoise Ponci ◽  
Martine Bobst ◽  
Pierre De Grandi ◽  
Denise Nardelli-Haefliger
Keyword(s):  
Neutralizing Antibodies ◽  
Hpv Infection ◽  
Oral Immunization ◽  
Human Papillomaviruses ◽  
Effective Vaccine ◽  
Virus Like Particle ◽  
Serovar Typhimurium ◽  
New Generation

ABSTRACT Cervical cancer results from cervical infection by human papillomaviruses (HPVs), especially HPV16. An effective vaccine against these HPVs is expected to have a dramatic impact on the incidence of this cancer and its precursor lesions. The leading candidate, a subunit prophylactic HPV virus-like particle (VLP) vaccine, can protect women from HPV infection. An alternative improved vaccine that avoids parenteral injection, that is efficient with a single dose, and that induces mucosal immunity might greatly facilitate vaccine implementation in different settings. In this study, we have constructed a new generation of recombinant Salmonella organisms that assemble HPV16 VLPs and induce high titers of neutralizing antibodies in mice after a single nasal or oral immunization with live bacteria. This was achieved through the expression of a HPV16 L1 capsid gene whose codon usage was optimized to fit with the most frequently used codons in Salmonella. Interestingly, the high immunogenicity of the new recombinant bacteria did not correlate with an increased expression of L1 VLPs but with a greater stability of the L1-expressing plasmid in vitro and in vivo in absence of antibiotic selection. Anti-HPV16 humoral and neutralizing responses were also observed with different Salmonella enterica serovar Typhimurium strains whose attenuating deletions have already been shown to be safe after oral vaccination of humans. Thus, our findings are a promising improvement toward a vaccine strain that could be tested in human volunteers.

scholarly journals Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

2021 ◽  
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anatomical Site ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.

scholarly journals SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood from the San Francisco Bay Area

2020 ◽  
Author(s):  
Dianna L. Ng ◽  
Gregory M. Goldgof ◽  
Brian R. Shy ◽  
Andrew G. Levine ◽  
Joanna Balcerek ◽  
...  
Keyword(s):  
San Francisco ◽  
Immunoglobulin G ◽  
Neutralizing Antibodies ◽  
San Francisco Bay ◽  
San Francisco Bay Area ◽  
Neutralizing Antibody ◽  
Immunoglobulin M ◽  
Bay Area ◽  
Antibody Titers

ABSTRACTWe report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally describe the longitudinal dynamics of immunoglobulin-G, immunoglobulin-M, and in vitro neutralizing antibody titers in COVID-19 patients. Neutralizing antibodies rise in tandem with immunoglobulin levels following symptom onset, exhibiting median time to seroconversion within one day of each other, and there is >93% positive percent agreement between detection of immunoglobulin-G and neutralizing titers.

scholarly journals SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dianna L. Ng ◽  
Gregory M. Goldgof ◽  
Brian R. Shy ◽  
Andrew G. Levine ◽  
Joanna Balcerek ◽  
...  
Keyword(s):  
San Francisco ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Immunoglobulin M ◽  
Bay Area ◽  
Neutralizing Capacity ◽  
Antibody Titers ◽  
Different Populations ◽  
Low Prevalence

Abstract Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.

scholarly journals Shedding of infectious SARS-CoV-2 by hospitalized COVID-19 patients in relation to serum antibody responses

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hedvig Glans ◽  
Sara Gredmark-Russ ◽  
Mikaela Olausson ◽  
Sara Falck-Jones ◽  
Renata Varnaite ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Neutralizing Antibody ◽  
University Hospital ◽  
Pcr Analysis ◽  
Symptom Duration ◽  
Cross Sectional ◽  
Antibody Titers ◽  
Specific Igg

Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic. The understanding of the transmission and the duration of viral shedding in SARS-CoV-2 infection is still limited. Objectives To assess the timeframe and potential risk of SARS-CoV-2 transmission from hospitalized COVID-19 patients in relation to antibody response. Method We performed a cross-sectional study of 36 COVID-19 patients hospitalized at Karolinska University Hospital. Patients with more than 8 days of symptom duration were sampled from airways, for PCR analysis of SARS-CoV-2 RNA and in vitro culture of replicating virus. Serum SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies titers were assessed by immunofluorescence assay (IFA) and microneutralization assay. Results SARS-CoV-2 RNA was detected in airway samples in 23 patients (symptom duration median 15 days, range 9–53 days), whereas 13 patients were SARS-CoV-2 RNA negative (symptom duration median 21 days, range 10–37 days). Replicating virus was detected in samples from 4 patients at 9–16 days. All but two patients had detectable levels of SARS-CoV-2-specific IgG in serum, and SARS-CoV-2 neutralizing antibodies were detected in 33 out of 36 patients. Total SARS-CoV-2-specific IgG titers and neutralizing antibody titers were positively correlated. High levels of both total IgG and neutralizing antibody titers were observed in patients sampled later after symptom onset and in patients where replicating virus could not be detected. Conclusions Our data suggest that the presence of SARS-Cov-2 specific antibodies in serum may indicate a lower risk of shedding infectious SARS-CoV-2 by hospitalized COVID-19 patients.

scholarly journals Glycan-masking spike antigen in NTD and RBD elicits broadly neutralizing antibodies against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Wei-Shuo Lin ◽  
I-Chen Chen ◽  
Hui-Chen Chen ◽  
Yi-Chien Lee ◽  
Suh-Chin Wu
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Vaccine Antigen ◽  
Broadly Neutralizing Antibodies ◽  
Neutralization Titer ◽  
Cell Responses ◽  
Folded Structure ◽  
Antibody Titers ◽  
The Impact

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired/undesired epitopes, without affecting the antigen overall-folded structure. This study examine the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N-Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N-Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.

scholarly journals Determination of a Statistically Valid Neutralization Titer in Plasma That Confers Protection against Simian-Human Immunodeficiency Virus Challenge following Passive Transfer of High-Titered Neutralizing Antibodies

2002 ◽  
Vol 76 (5) ◽  
pp. 2123-2130 ◽  
Author(s):  
Yoshiaki Nishimura ◽  
Tatsuhiko Igarashi ◽  
Nancy Haigwood ◽  
Reza Sadjadpour ◽  
Ron J. Plishka ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymph Node ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Passive Transfer ◽  
Neutralization Titer ◽  
Peripheral Blood Mononuclear ◽  
Vitro Assay ◽  
Immunodeficiency Virus

ABSTRACT We previously reported that high-titered neutralizing antibodies directed against the human immunodeficiency virus type 1 (HIV-1) envelope can block the establishment of a simian immunodeficiency virus (SIV)/HIV chimeric virus (SHIV) infection in two monkeys following passive transfer (R. Shibata et al., Nat. Med. 5:204-210, 1999). In the present study, increasing amounts of neutralizing immunoglobulin G (IgG) were administered to 15 pig-tailed macaques in order to obtain a statistically valid protective neutralization endpoint titer in plasma. Using an in vitro assay which measures complete neutralization of the challenge SHIV, we correlated the titers of neutralizing antibodies in plasma at the time of virus inoculation (which ranged from 1:3 to 1:123) with the establishment of infection in virus-challenged animals. Ten of 15 monkeys in the present experiment were virus free as a result of neutralizing IgG administration as monitored by DNA PCR (peripheral blood mononuclear cells and lymph node cells), RNA PCR (plasma), virus isolation, and the transfer of lymph node cell suspensions (108 cells) plus 8 ml of whole blood from protected animals to naïve macaques. The titer of neutralizing antibodies in the plasma calculated to protect 99% of virus-challenged monkeys was 1:38.

scholarly journals In Vitro Construction of Pseudovirions of Human Papillomavirus Type 16: Incorporation of Plasmid DNA into Reassembled L1/L2 Capsids

1998 ◽  
Vol 72 (12) ◽  
pp. 10298-10300 ◽  
Author(s):  
Kei Kawana ◽  
Hiroyuki Yoshikawa ◽  
Yuji Taketani ◽  
Kunito Yoshiike ◽  
Tadahito Kanda
Keyword(s):  
Plasmid Dna ◽  
Neutralizing Antibodies ◽  
Human Papillomaviruses ◽  
Expression Plasmid ◽  
Free System ◽  
Human Papillomavirus Type 16 ◽  
A Cell ◽  
Exogenous Genes ◽  
L1 And L2

ABSTRACT Lack of permissive and productive cell cultures for the human papillomaviruses (HPVs) has hindered the study of virus-neutralizing antibodies and infection. We developed a cell-free system generating infectious HPV16 pseudovirions. HPV16 L1/L2 capsids, which had been self-assembled in insect cells (Sf9) expressing virion proteins L1 and L2, were disassembled with 2-mercaptoethanol (2-ME), a reducing agent, and reassembled by removal of 2-ME in the presence of a β-galactosidase expression plasmid. Plasmid DNA purified together with the reassembled capsids was resistant to DNase I digestion. The reassembled pseudovirions mediated DNA transfer to COS-1 cells, as monitored by induced β-galactosidase activity. Transfer was inhibited by anti-HPV16 L1 antiserum but not by antisera against L1s of HPV6 and HPV18. Construction in vitro of HPV pseudovirions containing marker plasmids would be potentially useful in developing methods to assay virus-neutralizing antibodies and to transfer exogenous genes to HPV-susceptible cells.

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