scholarly journals Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency Virus

2000 ◽  
Vol 74 (20) ◽  
pp. 9403-9411 ◽  
Author(s):  
Margaret J. Hosie ◽  
Thomas Dunsford ◽  
Dieter Klein ◽  
Brian J. Willett ◽  
Celia Cannon ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Complete Protection ◽  
Virus Load ◽  
Virus Particles ◽  
Virulent Isolate ◽  
Load Following ◽  
Immunodeficiency Virus ◽  
Attenuated Isolate

ABSTRACT It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIVPET) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIVAM6 and FIVGL8. This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIVGL8-infected cats. In contrast, DNA vaccines based on either FIVPET or FIVGL8, which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIVPET but had no measurable effect on virus load when the infecting virus was FIVGL8. These results indicate that the more virulent FIVGL8 is intrinsically more resistant to vaccinal immunity than the FIVPET strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.

scholarly journals Role of Env in Resistance of Feline Immunodeficiency Virus (FIV)-Infected Cats to Superinfection by a Second FIV Strain as Determined by Using a Chimeric Virus

2007 ◽  
Vol 81 (19) ◽  
pp. 10474-10485 ◽  
Author(s):  
Simone Giannecchini ◽  
Mauro Pistello ◽  
Patrizia Isola ◽  
Donatella Matteucci ◽  
Paola Mazzetti ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Viral Envelope ◽  
Lymphoid Cells ◽  
Time Interval ◽  
Complete Protection ◽  
Challenge Virus ◽  
Immunodeficiency Virus

ABSTRACT A more or less pronounced resistance to superinfection by a second strain of the infecting virus has been observed in many lentivirus-infected hosts. We used a chimeric feline immunodeficiency virus (FIV), designated FIVχ, containing a large part of the env gene of a clade B virus (strain M2) and all the rest of the genome of a clade A virus (a p34TF10 molecular clone of the Petaluma strain modified to grow in lymphoid cells), to gain insights into such resistance. FIVχ was infectious and moderately pathogenic for cats and in vitro exhibited the neutralization specificity of the env donor. The experiments performed were bidirectional, in that cats preinfected with either parental virus were challenged with FIVχ and vice versa. The preinfected animals were partially or completely protected relative to what was observed in naïve control animals, most likely due, at least in part, to the circumstance that in all the preinfecting/challenge virus combinations examined, the first and the second virus shared significant viral components. Based on the proportions of complete protection observed, the role of a strongly matched viral envelope appeared to be modest and possibly dependent on the time interval between the first and the second infection. Furthermore, complete protection and the presence of measurable neutralizing antibodies capable of blocking the second virus in vitro were not associated.

scholarly journals Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies

Vaccine ◽  
2014 ◽  
Vol 32 (6) ◽  
pp. 746-754 ◽  
Author(s):  
James K. Coleman ◽  
Ruiyu Pu ◽  
Marcus M. Martin ◽  
Ezra N. Noon-Song ◽  
Raphael Zwijnenberg ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Vaccine Efficacy ◽  
Neutralizing Antibodies ◽  
Immunodeficiency Virus

scholarly journals Rectal Acquisition of Simian Immunodeficiency Virus (SIV) SIVmac239 Infection despite Vaccine-Induced Immune Responses against the Entire SIV Proteome

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Mauricio A. Martins ◽  
Lucas Gonzalez-Nieto ◽  
Michael J. Ricciardi ◽  
Varian K. Bailey ◽  
Christine M. Dang ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Vaccine Efficacy ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Hiv Vaccine ◽  
Partial Control ◽  
Immunodeficiency Virus

ABSTRACT Given the complex biology of human immunodeficiency virus (HIV) and its remarkable capacity to evade host immune responses, HIV vaccine efficacy may benefit from the induction of both humoral and cellular immune responses of maximal breadth, potency, and longevity. Guided by this rationale, we set out to develop an immunization protocol aimed at maximizing the induction of anti-Envelope (anti-Env) antibodies and CD8+ T cells targeting non-Env epitopes in rhesus macaques (RMs). Our approach was to deliver the entire simian immunodeficiency virus (SIV) proteome by serial vaccinations. To that end, 12 RMs were vaccinated over 81 weeks with DNA, modified vaccinia Ankara (MVA), vesicular stomatitis virus (VSV), adenovirus type 5 (Ad5), rhesus monkey rhadinovirus (RRV), and DNA again. Both the RRV and the final DNA boosters delivered a near-full-length SIVmac239 genome capable of assembling noninfectious SIV particles and inducing T-cell responses against all nine SIV proteins. Compared to previous SIV vaccine trials, the present DNA-MVA-VSV-Ad5-RRV-DNA regimen resulted in comparable levels of Env-binding antibodies and SIV-specific CD8+ T-cells. Interestingly, one vaccinee developed low titers of neutralizing antibodies (NAbs) against SIVmac239, a tier 3 virus. Following repeated intrarectal marginal-dose challenges with SIVmac239, vaccinees were not protected from SIV acquisition but manifested partial control of viremia. Strikingly, the animal with the low-titer vaccine-induced anti-SIVmac239 NAb response acquired infection after the first SIVmac239 exposure. Collectively, these results highlight the difficulties in eliciting protective immunity against immunodeficiency virus infection. IMPORTANCE Our results are relevant to HIV vaccine development efforts because they suggest that increasing the number of booster immunizations or delivering additional viral antigens may not necessarily improve vaccine efficacy against immunodeficiency virus infection.

scholarly journals Broadly neutralizing antibodies and vaccine design against HIV-1 infection

2019 ◽  
Vol 14 (1) ◽  
pp. 30-42 ◽  
Author(s):  
Qian Wang ◽  
Linqi Zhang
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vaccine Design ◽  
Therapeutic Interventions ◽  
Type I ◽  
Broadly Neutralizing Antibodies ◽  
Dynamic Studies ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Remarkable Progress

AbstractRemarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I (HIV-1) through antiretroviral therapy. However, vaccine development has remained challenging. Recent discoveries in broadly neutralizing monoclonal antibodies (bNAbs) has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response. Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein (Env) during infection. Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development.

scholarly journals Reverse Immunology Approach to Define a New HIV-gp41-Neutralizing Epitope

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Karim Dorgham ◽  
Nicolas Pietrancosta ◽  
Amel Affoune ◽  
Olivier Lucar ◽  
Tahar Bouceba ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Molecular Design ◽  
Docking Studies ◽  
Viral Envelope ◽  
Broadly Neutralizing Antibodies ◽  
Immunodeficiency Virus ◽  
Surface Envelope ◽  
Hiv 1

The design of immunogens susceptible to elicit potent and broadly neutralizing antibodies against the human immunodeficiency virus type 1 (HIV-1) remains a veritable challenge in the course of vaccine development. Viral envelope proteins adopt different conformational states during the entry process, allowing the presentation of transient neutralizing epitopes. We focused on the highly conserved 3S motif of gp41, which is exposed to the surface envelope in its trimeric prefusion state. Vaccination with a W614A-modified 3S peptide induces in animals neutralizing anti-HIV-1 antibodies among which we selected clone F8. We used F8 as bait to select for W614A-3S phage-peptide mimics. Binding and molecular docking studies revealed that F8 interacts similarly with W614A-3S and a Mim_F8-1 mimotope, despite their lack of sequence homology, suggesting structural mimicry. Finally, vaccination of mice with the purified Mim_F8-1 phage elicited HIV-1-neutralizing antibodies that bound to the cognate W614A-3S motif. Collectively, our findings provide new insights into the molecular design of immunogens to elicit antibodies with neutralizing properties.

scholarly journals Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus

2005 ◽  
Vol 79 (13) ◽  
pp. 8237-8242 ◽  
Author(s):  
Kathleen A. Hayes ◽  
Sadi Köksoy ◽  
Andrew J. Phipps ◽  
Wayne R. Buck ◽  
Gary J. Kociba ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Feline Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Significant Loss ◽  
Ctl Response ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load ◽  
Lymphocyte Responses ◽  
Ctl Responses

ABSTRACT To what extent the thymus is needed to preserve the virus-specific cytotoxic T-lymphocyte (CTL) response of lentivirus-infected adults is unclear. Presented here is the first definitive study using thymectomized (ThX) animals to directly evaluate the contribution of thymic function to lentivirus-specific CTL response and the control of lentivirus infections. ThX and mock-ThX cats were inoculated with feline immunodeficiency virus (FIV) and monitored for their FIV-specific CTL responses. Early in infection, both FIV-ThX and FIV-mock-ThX cats produced similar CTL responses, but surprisingly, after 20 weeks, the FIV-ThX cats showed a statistically significant loss of FIV-specific CTL activity, while FIV-infected cats with intact thymuses continued to maintain FIV-specific CTL. The loss of CTL did not affect plasma virus load, which remained elevated for both groups. These results emphasize the importance of thymic integrity in maintaining immunity to lentiviruses, but also bring into question the notion that virus load is regulated predominantly by the virus-specific CTL response.

Simple in vitro methods for titrating Feline Immunodeficiency Virus (FIV) and FIV neutralizing antibodies

1992 ◽  
Vol 37 (3) ◽  
pp. 241-252 ◽  
Author(s):  
Franco Tozzini ◽  
Donatella Matteucci ◽  
Patrizia Bandecchi ◽  
Fulvia Baldinotti ◽  
Alessandro Poli ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
In Vitro Methods ◽  
Immunodeficiency Virus

scholarly journals Comparative Immunogenicity of Subtype A Human Immunodeficiency Virus Type 1 Envelope Exhibiting Differential Exposure of Conserved Neutralization Epitopes

2009 ◽  
Vol 84 (5) ◽  
pp. 2573-2584 ◽  
Author(s):  
Catherine A. Blish ◽  
D. Noah Sather ◽  
George Sellhorn ◽  
Leonidas Stamatatos ◽  
Yide Sun ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Immunodeficiency Virus ◽  
Cd4 Binding Site ◽  
Variable Loops ◽  
Linear Epitopes ◽  
Subtype A ◽  
Hiv 1

ABSTRACT Development of broadly cross-reactive neutralizing antibodies (NAbs) remains a major goal of HIV-1 vaccine development, but most candidate envelope immunogens have had limited ability to cross-neutralize heterologous strains. To evaluate the immunogenicity of subtype A variants of HIV-1, rabbits were immunized with pairs of closely related subtype A envelopes from the same individual. In each immunogen pair, one variant was readily neutralized by a variety of monoclonal antibodies and plasma antibodies, while the other was neutralization resistant, suggesting differences in the exposures of key epitopes. The breadth of the antibody response was evaluated against subtype A, B, C, and D variants of HIV-1. The specificity of the immunogen-derived neutralizing antibody response was also compared to that of the infected individuals from whom these variants were cloned. None of the immunogens produced broad neutralizing antibodies in immunized animals, and most of the neutralizing antibodies were directed to the variable loops, particularly the V3 loop. No detectable antibodies to either of the potentially exposed conserved epitopes, the membrane proximal external region, or the CD4 binding site were found with immunized rabbits. In contrast, relatively little of the neutralizing activity within the plasma samples of the infected individuals was directed to linear epitopes within the variable loops. These data indicate that immunogens designed to expose conserved regions did not enhance generation of broadly neutralizing antibodies in comparison with the immunogens that failed to expose those regions using this immunization approach.

scholarly journals AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Homologous Erythrocytes as a Delivery System for Preferential Immunization with Putative Protective Antigens

1998 ◽  
Vol 5 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Laura Chiarantini ◽  
Donatella Matteucci ◽  
Mauro Pistello ◽  
Umberto Mancini ◽  
Paola Mazzetti ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Vaccine Development ◽  
Ex Vivo ◽  
Degree Of Protection ◽  
Aids Vaccine ◽  
Protective Antigens ◽  
Homologous Virus ◽  
Immunodeficiency Virus ◽  
Specific Pathogen

ABSTRACT Feline immunodeficiency virus (FIV) is a useful model for testing of criteria for AIDS vaccine development. In the protocol we adopted, we used a primary isolate of FIV as a source of antigen and, for challenge, plasma from cats infected with the homologous virus never passaged in vitro. Cat erythrocytes (RBC) were coated with the surface components of freshly harvested and purified FIV by means of biotin-avidin-biotin bridges and used to immunize specific-pathogen-free cats (four doses at monthly intervals; total amount of FIV antigen administered per cat, approximately 14 μg). Immunized cats developed moderate levels of antibodies directed mainly to surface components of the virion and clearly evident lymphoproliferative responses. Four months after the last dose of immunogen, FIV-immunized cats and control cats immunized with bovine serum albumin-coated RBC were challenged. Judged from the results of the subsequent 12-month follow-up, FIV-immunized cats exhibited at least some degree of protection. However, following rechallenge, most of the FIV-immunized animals became virus positive in spite of a booster immunogen dose given 2 months before the second challenge.

Development of a Norovirus P Particle Platform for Eliciting Neutralizing Antibody Responses to the Membrane Proximal External Region of Human Immunodeficiency Virus Type 1 Envelope

2014 ◽  
Vol 21 (12) ◽  
pp. 1230-1239
Author(s):  
Yang Zang ◽  
Jinpeng Bi ◽  
Dongchuan Du ◽  
Xintao Liu ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibodies ◽  
External Region ◽  
Membrane Proximal External Region ◽  
Immunodeficiency Virus ◽  
Hiv 1

Eliciting efficient broadly neutralizing antibodies (BnAbs) is an important goal that has yet to be achieved for human immunodeficiency type 1 (HIV-1) vaccine development, although they are rarely produced in virus-infected individuals. In particular, inducing specific neutralizing antibodies to the gp41 membrane proximal external region (MPER) has proven a difficult task. In this study, we introduce Norovirus P particles as a new platform to display the MPER epitope of HIV-1 as a vaccine with the aim of enhancing immune responses. The results showed that HIV-1 chimeric P particles were capable of inducing MPER-specific antibody responses in immunized guinea pigs, although only weakly neutralizing activity could be detected. These findings are consistent with other previous studies which have also focused on the well-studied 2F5 and 4E10 BnAbs. Our findings provide an alternate strategy for design of vaccines against HIV-1. However, great challenges remain in the effort to develop vaccines that can induce efficient HIV-1 neutralizing antibodies.

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