scholarly journals 259. Prevalence and Correlation of Neutralizing Antibodies Against AAV2, 7, 8, 9 and RH32.33 in the Human Sera from Southern China

2012 ◽  
Vol 20 ◽  
pp. S102
2015 ◽  
Vol 89 (14) ◽  
pp. 7348-7362 ◽  
Author(s):  
Wen-Yang Tsai ◽  
Anna Durbin ◽  
Jih-Jin Tsai ◽  
Szu-Chia Hsieh ◽  
Stephen Whitehead ◽  
...  

ABSTRACTThe four serotypes of dengue virus (DENV) cause the most important and rapidly emerging arboviral diseases in humans. The recent phase 2b and 3 studies of a tetravalent dengue vaccine reported a moderate efficacy despite the presence of neutralizing antibodies, highlighting the need for a better understanding of neutralizing antibodies in polyclonal human sera. Certain type-specific (TS) antibodies were recently discovered to account for the monotypic neutralizing activity and protection after primary DENV infection. The nature of neutralizing antibodies after secondary DENV infection remains largely unknown. In this study, we examined sera from 10 vaccinees with well-documented exposure to first and second DENV serotypes through heterotypic immunization with live-attenuated vaccines. Higher serum IgG avidities to both exposed and nonexposed serotypes were found after secondary immunization than after primary immunization. Using a two-step depletion protocol to remove different anti-envelope antibodies, including group-reactive (GR) and complex-reactive (CR) antibodies separately, we found GR and CR antibodies together contributed to more than 50% of neutralizing activities against multiple serotypes after secondary immunization. Similar findings were demonstrated in patients after secondary infection. Anti-envelope antibodies recognizing previously exposed serotypes consisted of a large proportion of GR antibodies, CR antibodies, and a small proportion of TS antibodies, whereas those recognizing nonexposed serotypes consisted of GR and CR antibodies. These findings have implications for sequential heterotypic immunization or primary immunization of DENV-primed individuals as alternative strategies for DENV vaccination. The complexity of neutralizing antibodies after secondary infection provides new insights into the difficulty of their application as surrogates of protection.IMPORTANCEThe four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Despite the presence of neutralizing antibodies, a moderate efficacy was recently reported in phase 2b and 3 trials of a dengue vaccine; a better understanding of neutralizing antibodies in polyclonal human sera is urgently needed. We studied vaccinees who received heterotypic immunization of live-attenuated vaccines, as they were known to have received the first and second DENV serotype exposures. We found anti-envelope antibodies consist of group-reactive (GR), complex-reactive (CR), and type-specific (TS) antibodies, and that both GR and CR antibodies contribute significantly to multitypic neutralizing activities after secondary DENV immunization. These findings have implications for alternative strategies for DENV vaccination. Certain TS antibodies were recently discovered to contribute to the monotypic neutralizing activity and protection after primary DENV infection; our findings of the complexity of neutralizing activities after secondary immunization/infection provide new insights for neutralizing antibodies as surrogates of protection.


1936 ◽  
Vol 63 (5) ◽  
pp. 655-668 ◽  
Author(s):  
Thomas Francis ◽  
T. P. Magill

The results of mouse protection tests with 136 human sera and a strain of human influenza virus are described. After the 1st year of life, the sera of approximately half the individuals tested contained sufficient antibody to furnish complete protection to mice. A much higher percentage of the sera obtained from individuals recently convalescent from influenza exerted a completely protective effect. On the other hand, certain sera protected only partially under the conditions of the tests. The results have been compared with those obtained by Shope in tests done with the same sera against swine influenza virus. The possible epidemiological significance of the results is discussed.


2005 ◽  
Vol 130 (1-2) ◽  
pp. 15-21 ◽  
Author(s):  
Osnat Eyal ◽  
Udy Olshevsky ◽  
Shlomo Lustig ◽  
Nir Paran ◽  
Menachem Halevy ◽  
...  

2005 ◽  
Vol 86 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Sabine Santibanez ◽  
Stefan Niewiesk ◽  
Alla Heider ◽  
Jürgen Schneider-Schaulies ◽  
Guy A. M. Berbers ◽  
...  

Measles virus (MV) infection and vaccination induce long-lasting immunity and neutralizing-antibody responses that are directed against the MV haemagglutinin (H) and the fusion (F) protein. A new MV genotype, D7, emerged recently in western Germany and rapidly replaced the long-term endemically circulating genotypes C2 and D6. Analysis of the H gene of C2, D6, D7 and vaccine viruses revealed uniform sequences for each genotype. Interestingly, a consistent exchange of seven distinct amino acids in the D7 H was observed when compared with residues shared between C2, D6 and vaccine viruses, and one exchange (D416→N) in the D7 H was associated with an additional N-linked glycosylation. In contrast, the F gene is highly conserved between MVs of these genotypes. To test whether the D7 H protein escapes from antibody responses that were raised against earlier circulating or vaccine viruses, the neutralizing capacity of mAbs recognizing seven distinct domains on the H of an Edmonston-related MV was compared. The mAbs revealed a selective and complete loss of two neutralizing epitopes on the D7 H when compared with C2, D6 and vaccine viruses. To assess whether these alterations of the D7 H affect the neutralizing capacity of polyclonal B-cell responses, genotype-specific antisera were produced in cotton rats. However, no significant genotype-dependent difference was found. Likewise, human sera obtained from vaccinees (n=7) and convalescents (n=6) did not distinguish between the MV genotypes. Although the hypothesis of selection of D7 viruses by pre-existing neutralizing antibodies is compatible with the differing pattern of neutralizing epitopes on the H protein, it was not confirmed by the results of MV neutralization with polyclonal sera.


Author(s):  
Zhuoming Liu ◽  
Laura A. VanBlargan ◽  
Paul W. Rothlauf ◽  
Louis-Marie Bloyet ◽  
Rita E. Chen ◽  
...  

ABSTRACTAlthough neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of most COVID-19 vaccines and being developed as therapeutics, escape mutations could compromise such countermeasures. To define the immune-mediated mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor binding domain (RBD) to generate 48 escape mutants. These variants were mapped onto the RBD structure and evaluated for cross-resistance by convalescent human plasma. Although each mAb had unique resistance profiles, many shared residues within an epitope, as several variants were resistant to multiple mAbs. Remarkably, we identified mutants that escaped neutralization by convalescent human sera, suggesting that some humans induce a narrow repertoire of neutralizing antibodies. By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, we identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans.


2006 ◽  
Vol 87 (9) ◽  
pp. 2577-2581 ◽  
Author(s):  
Cécile Voisset ◽  
Anne Op de Beeck ◽  
Pauline Horellou ◽  
Marlène Dreux ◽  
Thierry Gustot ◽  
...  

The neutralizing activity of anti-hepatitis C virus (HCV) antibodies is attenuated by a factor present in human sera, which has been proposed to be high-density lipoproteins (HDLs). HDLs have also been shown to facilitate the entry of HCV pseudoparticles (HCVpp) into target cells. Here, the aim of the study was to determine whether HDL-mediated facilitation of HCVpp and infectious HCV (HCVcc) entry and attenuation of neutralization are two related phenomena. The data indicated that HDLs attenuate neutralization at a constant rate. In addition, as for HDL-mediated facilitation of HCVpp entry, attenuation of neutralization depended on the expression of the scavenger receptor BI (SR-BI) and its selective lipid-uptake function. Finally, kinetic experiments showed that HDL-mediated facilitation of HCVpp entry is more rapid than virus neutralization. Altogether, these observations indicate that HCV is exploiting the physiological activity of SR-BI for promoting its entry into target cells, which consequently also protects the virus against neutralizing antibodies.


1998 ◽  
Vol 72 (9) ◽  
pp. 7099-7107 ◽  
Author(s):  
Eun Ju Park ◽  
Luba K. Vujcic ◽  
Rita Anand ◽  
Theodore S. Theodore ◽  
Gerald V. Quinnan

ABSTRACT The escape of human immunodeficiency virus type 1 from effects of neutralizing antibodies was studied by using neutralization-resistant (NR) variants generated by growing the neutralization-sensitive (NS) wild-type MN virus in the presence of human serum with neutralizing antibodies, more than 99% of which were directed at the V3 region of gp120. The variants obtained had broad neutralization resistance to human sera, without limitation with respect to the V3 specificity of the sera. The molecular basis for the resistance was evaluated with molecularly cloned viruses, as well as with pseudoviruses expressing envelope glycoproteins of the NS and NR phenotypes. Nucleotide sequence analyses comparing NS and NR clones revealed a number of polymorphisms, including six in the V1/V2 region, two in C4/V5 of gp120, three in the leucine zipper (LZ) domain of gp41, and two in the second external putative α-helix region of gp41. A series of chimeras from NS and NRenv genes was constructed, and each was presented on pseudoviruses to locate the domain(s) which conferred the phenotypic changes. The neutralization phenotypes of the chimeric clones were found to be dependent on mutations in both the C4/V5 region of gp120 and the LZ region of gp41. Additionally, interaction between mutations in gp120 and gp41 was demonstrated in that a chimeric envgene consisting of a gp120 coding sequence from an NS clone and a gp41 sequence from an NR clone yielded a pseudovirus with minimal infectivity. The possible significance of predicted amino acid changes in these domains is discussed. The results indicate that polyvalent antibodies predominantly directed against V3 can induce NR through selection for mutations that alter interactions of other domains in the envelope complex.


2003 ◽  
Vol 45 (2) ◽  
pp. 109-110 ◽  
Author(s):  
Luis Adrián Diaz ◽  
Lorena Ivana Spinsanti ◽  
Walter Ricardo Almiron ◽  
Marta Silvia Contigiani

Una virus (UNAV), Togaviridae family, is widely distributed in South America, where infections have been detected in mosquitoes and vertebrate hosts (humans, birds and horses). We analyzed human sera from Córdoba inhabitants aged 44 to 89 years and using a neutralization test, we found a prevalence of UNAV antibodies of 3.8% (3/79). The low titers detected suggest past infections probably acquired in rural areas of the Province of Córdoba (central Argentina). None sera were found positive for MAYV neutralizing antibodies. This is the first report of human infections by UNAV in Argentina.


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