scholarly journals Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors

2017 ◽  
Author(s):  
Sophie M. Andrews ◽  
Yonghong Zhang ◽  
Tao Dong ◽  
Sarah L. Rowland-Jones ◽  
Sunetra Gupta ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Acid Sites ◽  
Humoral Immune ◽  
Founder Virus ◽  
Distal Edge ◽  
Host Genetic ◽  
Significant Positive Selection ◽  
Antibody Epitopes ◽  
Hiv 1 ◽  
Major Target

ABSTRACTThe HIV-1 envelope protein mutates rapidly to evade recognition and killing, and is a major target of the humoral immune response and in vaccine development. Identification of common antibody epitopes for vaccine development have been complicated by large variations on both virus (different infecting founder strains) and host genetic levels. We studied HIV-1 envelopegp120evolution in 12 Chinese former plasma donors infected with a purportedly single founder virus, with the aim of identifying common antibody epitopes under immune selection. We found five amino acid sites to be under significant positive selection in ≥50% of the patients, and 22 sites housing mutations consistent with antibody-mediated selection. Despite strong selection pressure, some sites housed a limited repertoire of amino acids. Structural modelling revealed that most sites were located on the exposed distal edge of the Gp120 trimer, whilst wholly invariant sites clustered within the centre of the protein complex. Four sites, flanking the V3 hypervariable loop of the Gp120, represent novel antibody epitopes that may be suitable as vaccine candidates.

scholarly journals Evolutionary Pattern of Asian HIV-1 Subtype B from 1990 to 2007:In SilicoAnalysis Based on Envelop Protein

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Sobia Kanwal ◽  
Tariq Mahmood
Keyword(s):  
Vaccine Development ◽  
V3 Loop ◽  
Multiple Sequence ◽  
Evolutionary Pattern ◽  
Subtype B ◽  
Glycosylation Sites ◽  
Mutation Pattern ◽  
Hiv 1 ◽  
Fourth Position ◽  
Major Target

HIV-1 envelop gene is a major target for vaccine development. Envelop protein and its V3 loop is shown to be important determinant of HIV-1 pathogenecity. Herein, the evolutionary pattern of most prevalent HIV-1 subtype B in Asia is determined by analyzing envelop protein and V3 domain based on the 40 randomly selected sequences of HIV-1 from database (Los Alamos), divided into four groups since 1990–2007. Construction of envelop protein phylogeny by using MEGA 5 exhibit the active mutation pattern, increase in potential N-glycosylation sites which were predicted by using online software SignalP-NN. An online available tool Drawgram was used for multiple sequence alignment (MSA) of HIV-1 subtype B envelop region and V3 loop while the alignment was rechecked by using CLUSTAL W and further was analyzed for GPGX motif and conserved region in V3 loop. Variation at fourth position of the GPGX motif and 60% conservation was found in V3 loop. Hence, this diversifying pattern of envelop protein in the Asia formulates the HIV-1 strains more pathogenic during the period of 17 years. These findings might help in understanding significant structural and functional constrains of the mutant viral strains and ultimately in vaccine development.

scholarly journals Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response

2012 ◽  
Vol 2012 ◽  
pp. 1-16
Author(s):  
Raghavan Sampathkumar ◽  
Elnaz Shadabi ◽  
Ma Luo
Keyword(s):  
Genetic Variation ◽  
Vaccine Development ◽  
Therapy Response ◽  
Divergent Evolution ◽  
Sequence Database ◽  
Host Genetic ◽  
Per Se ◽  
Tremendous Challenge ◽  
Hiv 1 ◽  
Hiv Aids

As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomenaper seposes tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response.

HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

2020 ◽  
Vol 28 ◽  
Author(s):  
Alireza Milani ◽  
Kazem Baesi ◽  
Elnaz Agi ◽  
Ghazal Marouf ◽  
Maryam Ahmadi ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Treated Group ◽  
Vaccine Antigen ◽  
Accessory Proteins ◽  
Serological Method ◽  
Th2 Immune Response ◽  
Untreated Individuals ◽  
Immunogenic Properties ◽  
Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

scholarly journals Flavivirus NS1 and Its Potential in Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 622
Author(s):  
Kassandra L. Carpio ◽  
Alan D. T. Barrett
Keyword(s):  
Vaccine Development ◽  
Virus Assembly ◽  
Ns1 Protein ◽  
Human Pathogens ◽  
Unusual Structure ◽  
Replication Complex ◽  
Virus Challenge ◽  
Humoral Immune ◽  
Tick Borne Encephalitis ◽  
Flavivirus Infection

The Flavivirus genus contains many important human pathogens, including dengue, Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), yellow fever (YF) and Zika (ZIK) viruses. While there are effective vaccines for a few flavivirus diseases (JE, TBE and YF), the majority do not have vaccines, including WN and ZIK. The flavivirus nonstructural 1 (NS1) protein has an unusual structure–function because it is glycosylated and forms different structures to facilitate different roles intracellularly and extracellularly, including roles in the replication complex, assisting in virus assembly, and complement antagonism. It also plays a role in protective immunity through antibody-mediated cellular cytotoxicity, and anti-NS1 antibodies elicit passive protection in animal models against a virus challenge. Historically, NS1 has been used as a diagnostic marker for the flavivirus infection due to its complement fixing properties and specificity. Its role in disease pathogenesis, and the strong humoral immune response resulting from infection, makes NS1 an excellent target for inclusion in candidate flavivirus vaccines.

scholarly journals Role of Circulating Immune Complexes in the Pathogenesis of Canine Leishmaniasis: New Players in Vaccine Development

2021 ◽  
Vol 9 (4) ◽  
pp. 712
Author(s):  
Cristina Cacheiro-Llaguno ◽  
Nuria Parody ◽  
Marta R. Escutia ◽  
Jerónimo Carnés
Keyword(s):  
Immune Complexes ◽  
Vaccine Development ◽  
Correct Diagnosis ◽  
Circulating Immune Complexes ◽  
Response To Treatment ◽  
Canine Leishmaniasis ◽  
Leishmania Infection ◽  
Serum Samples ◽  
Humoral Immune

During canine visceral leishmaniasis (CanL), due to Leishmania infantum (L. infantum), uncontrolled infection leads to a strong humoral immune response. As a consequence of the production of high antibody levels and the prolonged presence of parasite antigens, circulating immune complexes (CIC) are formed, which can be deposited in certain organs and tissues, inducing vasculitis, uveitis, dermatitis and especially glomerulonephritis and renal failure. A method to detect CIC and quantify their levels in serum samples from dogs infected with L. infantum has been recently described. It allowed demonstration of a correlation between CIC levels and disease severity. Thus, CIC measurement may be useful for diagnosis, assessment of disease progression and monitoring response to treatment. This is an interesting finding, considering that there remains an urgent need for identification of novel biomarkers to achieve a correct diagnosis and for optimal disease staging of dogs suffering from Leishmania infection. The objective of the present review is to shed light on the role of CIC in CanL, as well as to highlight their potential use not only as diagnostic and prognostic biomarkers but also as a valuable tool in vaccine development and new immunotherapy strategies to prevent or control disease outcome.

scholarly journals SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

scholarly journals Immunogenicity of HIV-1-Based Virus-Like Particles with Increased Incorporation and Stability of Membrane-Bound Env

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 239
Author(s):  
Christopher A. Gonelli ◽  
Hannah A. D. King ◽  
Charlene Mackenzie ◽  
Secondo Sonza ◽  
Rob J. Center ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralization Activity ◽  
Virus Like Particles ◽  
Antibody Isotypes ◽  
Immunodeficiency Virus ◽  
Proline Substitution ◽  
Membrane Bound ◽  
Antibody Epitopes ◽  
Hiv 1

An optimal prophylactic vaccine to prevent human immunodeficiency virus (HIV-1) transmission should elicit protective antibody responses against the HIV-1 envelope glycoprotein (Env). Replication-incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present virion-associated Env with a native-like structure during vaccination that closely resembles that encountered on infectious virus. Here, we optimized the incorporation of Env into previously designed mature-form VLPs (mVLPs) and assessed their immunogenicity in mice. The incorporation of Env into mVLPs was increased by replacing the Env transmembrane and cytoplasmic tail domains with those of influenza haemagglutinin (HA-TMCT). Furthermore, Env was stabilized on the VLP surface by introducing an interchain disulfide and proline substitution (SOSIP) mutations typically employed to stabilize soluble Env trimers. The resulting mVLPs efficiently presented neutralizing antibody epitopes while minimizing exposure of non-neutralizing antibody sites. Vaccination of mice with mVLPs elicited a broader range of Env-specific antibody isotypes than Env presented on immature VLPs or extracellular vesicles. The mVLPs bearing HA-TMCT-modified Env consistently induced anti-Env antibody responses that mediated modest neutralization activity. These mVLPs are potentially useful immunogens for eliciting neutralizing antibody responses that target native Env epitopes on infectious HIV-1 virions.

scholarly journals Potent and Stable Attenuation of Live-HIV-1 by Gain of a Proteolysis-resistant Inhibitor of NF-κB (IκB-αS32/36A) and the Implications for Vaccine Development

1999 ◽  
Vol 274 (25) ◽  
pp. 17567-17572 ◽  
Author(s):  
Ileana Quinto ◽  
Massimo Mallardo ◽  
Francesca Baldassarre ◽  
Giuseppe Scala ◽  
George Englund ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Hiv 1

scholarly journals Scarcity or Absence of Humoral Immune Responses in the Plasma and Cervicovaginal Lavage Fluids of Heavily HIV-1-Exposed But Persistently Seronegative Women

2011 ◽  
Vol 27 (5) ◽  
pp. 469-486 ◽  
Author(s):  
Jiri Mestecky ◽  
Peter F. Wright ◽  
Lucia Lopalco ◽  
Herman F. Staats ◽  
Pamela A. Kozlowski ◽  
...  
Keyword(s):  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cervicovaginal Lavage ◽  
Hiv 1

scholarly journals Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape Processes in HIV-1 Infection

2015 ◽  
Vol 89 (20) ◽  
pp. 10303-10318 ◽  
Author(s):  
Justine E. Sunshine ◽  
Brendan B. Larsen ◽  
Brandon Maust ◽  
Ellie Casey ◽  
Wenje Deng ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Evolution ◽  
T Cell Responses ◽  
Fitness Cost ◽  
Viral Population ◽  
Cell Responses ◽  
Founder Virus ◽  
Ctl Escape ◽  
The Impact ◽  
Hiv 1

ABSTRACTTo understand the interplay between host cytotoxic T-lymphocyte (CTL) responses and the mechanisms by which HIV-1 evades them, we studied viral evolutionary patterns associated with host CTL responses in six linked transmission pairs. HIV-1 sequences corresponding to full-length p17 and p24gagwere generated by 454 pyrosequencing for all pairs near the time of transmission, and seroconverting partners were followed for a median of 847 days postinfection. T-cell responses were screened by gamma interferon/interleukin-2 (IFN-γ/IL-2) FluoroSpot using autologous peptide sets reflecting any Gag variant present in at least 5% of sequence reads in the individual's viral population. While we found little evidence for the occurrence of CTL reversions, CTL escape processes were found to be highly dynamic, with multiple epitope variants emerging simultaneously. We found a correlation between epitope entropy and the number of epitope variants per response (r= 0.43;P= 0.05). In cases in which multiple escape mutations developed within a targeted epitope, a variant with no fitness cost became fixed in the viral population. When multiple mutations within an epitope achieved fitness-balanced escape, these escape mutants were each maintained in the viral population. Additional mutations found to confer escape but undetected in viral populations incurred high fitness costs, suggesting that functional constraints limit the available sites tolerable to escape mutations. These results further our understanding of the impact of CTL escape and reversion from the founder virus in HIV infection and contribute to the identification of immunogenic Gag regions most vulnerable to a targeted T-cell attack.IMPORTANCERapid diversification of the viral population is a hallmark of HIV-1 infection, and understanding the selective forces driving the emergence of viral variants can provide critical insight into the interplay between host immune responses and viral evolution. We used deep sequencing to comprehensively follow viral evolution over time in six linked HIV transmission pairs. We then mapped T-cell responses to explore if mutations arose due to adaption to the host and found that escape processes were often highly dynamic, with multiple mutations arising within targeted epitopes. When we explored the impact of these mutations on replicative capacity, we found that dynamic escape processes only resolve with the selection of mutations that conferred escape with no fitness cost to the virus. These results provide further understanding of the complicated viral-host interactions that occur during early HIV-1 infection and may help inform the design of future vaccine immunogens.

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