scholarly journals Heterotypic Protection and Induction of a Broad Heterotypic Neutralization Response by Rotavirus-Like Particles

1999 ◽  
Vol 73 (6) ◽  
pp. 4813-4822 ◽  
Author(s):  
Sue E. Crawford ◽  
Mary K. Estes ◽  
Max Ciarlet ◽  
Christopher Barone ◽  
Christine M. O’Neal ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Diarrheal Disease ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Rotavirus Vaccines ◽  
Life Threatening ◽  
And Control ◽  
Potential Use ◽  
Neutralization Response

ABSTRACT The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11. Immunization with VLPs may provide sufficient priming of the immune system to induce protective anamnestic heterotypic neutralizing antibody responses upon subsequent rotavirus infection. Therefore, a limited number of serotypes of VLPs may be sufficient to provide a broadly protective subunit vaccine.

scholarly journals Magnitude of Serum and Intestinal Antibody Responses Induced by Sequential Replicating and Nonreplicating Rotavirus Vaccines in Gnotobiotic Pigs and Correlation with Protection

2004 ◽  
Vol 11 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Marli S. P. Azevedo ◽  
Lijuan Yuan ◽  
Cristiana Iosef ◽  
Kyeong-Ok Chang ◽  
Yunjeong Kim ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Vaccine Regimen ◽  
Rotavirus Vaccines ◽  
Antibody Titers ◽  
Iga Antibody ◽  
Gnotobiotic Pigs

ABSTRACT A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. Because serum or fecal antibody titers, but not intestinal ASC responses, can be used as potential markers of protective immunity in clinical vaccine trials, we determined the serum and intestinal antibody responses to this prime-boost rotavirus vaccine regimen and the correlations with protection. Gnotobiotic pigs were vaccinated with one of the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were also compared with three i.n. doses of VLP+mLT (VLP3x) and one and three oral doses of AttHRV (AttHRV1x and AttHRV3x, respectively). Before challenge all pigs in the AttHRV/VLP2x group seroconverted to positivity for serum immunoglobulin A (IgA) antibodies. The pigs in this group also had significantly higher (P < 0.05) intestinal IgA antibody titers pre- and postchallenge and IgG antibody titers postchallenge compared to those in the other groups. Statistical analyses of the correlations between serum IgM, IgA, IgG, and virus-neutralizing antibody titers and protection demonstrated that each of these was an indicator of protective immunity induced by the AttHRV3x and the AttHRV/VLP2x regimens. However, only IgA and not IgM or IgG antibody titers in serum were highly correlated (R 2 = 0.89; P < 0.001) with the corresponding isotype antibody (IgA) titers in the intestines among all the vaccinated groups, indicating that the IgA antibody titer is probably the most reliable indicator of protection.

scholarly journals Antibody responses in buffalos immunized with Clostridium perfringens beta and epsilon toxoids

2001 ◽  
Vol 46 (No. 9–10) ◽  
pp. 241-243 ◽  
Author(s):  
S. Rahman M ◽  
K. Baek B ◽  
T. Hong S ◽  
H. Lee J
Keyword(s):  
Antibody Titre ◽  
Clostridium Perfringens ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Control Group ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titres ◽  
Group A ◽  
And Control

The antibody responses to toxoids were measured to investigate whether&nbsp;Clostridium perfringens&nbsp;beta and epsilon toxoids induced protective humoral immune responses in buffalos. Total of 24 buffalos were divided into 4 groups (n&nbsp;= 6), beta toxoid, epsilon toxoid, combination and control groups. These buffalo groups were administered each of the designated toxoids. Immunizations in the beta and epsilon toxoid groups induced strong antibody responses. The neutralizing antibody titres from the beta and epsilon toxoid groups were equally log101.2 on day 21 after inoculation whereas there was no antibody titre detected from the control group. A statistically significant (P&nbsp;&lt; 0.01) increase in antibody titre was observed from day 0 to day 14 and 21 after inoculation. The antibody production did not vary significantly due to day of inoculation and toxoid interactions.

scholarly journals An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Martijn A. Langereis ◽  
Irina C. Albulescu ◽  
Judith Stammen-Vogelzangs ◽  
Morindy Lambregts ◽  
Ken Stachura ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Animal Species ◽  
Close Contact ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Replicon Particle ◽  
Nasal Swabs ◽  
Animal Hosts

AbstractEarly in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.

scholarly journals SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants

2020 ◽  
Author(s):  
Fiona Tea ◽  
Alberto Ospina Stella ◽  
Anupriya Aggarwal ◽  
David Ross Darley ◽  
Deepti Pilli ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Plasma Therapy ◽  
Nucleocapsid Proteins ◽  
Viral Neutralization ◽  
Serial Samples ◽  
High Responders ◽  
Neutralization Response ◽  
Selection Of

AbstractThe SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of ‘high responders’ maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.One Sentence SummaryNeutralizing antibody responses to SARS-CoV-2 are sustained, associated with COVID19 severity, and evaded by emerging viral variants

scholarly journals Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant

2021 ◽  
Author(s):  
Venkata-Viswanadh Edara ◽  
Lilin Lai ◽  
Malaya Sahoo ◽  
Katharine Floyd ◽  
Mamdouh Sibai ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Live Virus ◽  
Global Pandemic ◽  
Virus Assay ◽  
Recent Emergence ◽  
The World ◽  
Antibody Resistance ◽  
Second Wave

SARS-CoV-2 has caused a devastating global pandemic. The recent emergence of SARS-CoV-2 variants that are less sensitive to neutralization by convalescent sera or vaccine-induced neutralizing antibody responses has raised concerns. A second wave of SARS-CoV-2 infections in India is leading to the expansion of SARS-CoV-2 variants. The B.1.617.1 variant has rapidly spread throughout India and to several countries throughout the world. In this study, using a live virus assay, we describe the neutralizing antibody response to the B.1.617.1 variant in serum from infected and vaccinated individuals. We found that the B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from COVID-19 convalescent and Moderna and Pfizer vaccinated individuals. Despite this, a majority of the sera from convalescent individuals and all sera from vaccinated individuals were still able to neutralize the B.1.617.1 variant. This suggests that protective immunity by the mRNA vaccines tested here are likely retained against the B.1.617.1 variant. As the B.1.617.1 variant continues to evolve, it will be important to monitor how additional mutations within the spike impact antibody resistance, viral transmission and vaccine efficacy.

scholarly journals Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xin Xu ◽  
Sheng Nie ◽  
Yanqun Wang ◽  
Quanxin Long ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Half Time ◽  
Peak Titer ◽  
Neutralization Rate ◽  
Repeat Infection ◽  
Post Onset

AbstractOur understanding of the protective immunity, particularly the long-term dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2, is currently limited. We enrolled a cohort of 545 COVID-19 patients from Hubei, China, who were followed up up to 7 months, and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test (sVNT). In our validation study, sVNT IC50 titers and the neutralization rate measured at a single dilution (1:20) were well correlated with FRNT titers (r = 0.85 and 0.84, respectively). The median time to seroconversion of NAbs was 5.5 days post onset of symptoms. The rate of positive sVNT was 52% in the first week, reached 100% in the third week, and remained above 97% till 6 months post onset. Quantitatively, NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of >1000. NAbs declined with a half-time of 61 days (95% CI: 49–80 days) within the first two months, and the decay deaccelerated to a half-time of 104 days (95% CI: 86–130 days) afterward. The peak levels of NAbs were positively associated with severity of COVID-19 and age, while negatively associated with serum albumin levels. The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability. NAbs response positively correlated with disease severity, warning for the possibility of repeat infection in patients with mild COVID-19.

scholarly journals Parenterally Administered P24-VP8* Nanoparticle Vaccine Conferred Strong Protection against Rotavirus Diarrhea and Virus Shedding in Gnotobiotic Pigs

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 177 ◽  
Author(s):  
Ramesh ◽  
Mao ◽  
Lei ◽  
Twitchell ◽  
Shiraz ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
T Cell Response ◽  
Antibody Responses ◽  
Post Inoculation ◽  
Virus Shedding ◽  
Diarrhea Virus ◽  
Rotavirus Vaccines ◽  
Increased Risk ◽  
Rotavirus Diarrhea

Current live rotavirus vaccines are costly with increased risk of intussusception due to vaccine replication in the gut of vaccinated children. New vaccines with improved safety and cost-effectiveness are needed. In this study, we assessed the immunogenicity and protective efficacy of a novel P24-VP8* nanoparticle vaccine using the gnotobiotic (Gn) pig model of human rotavirus infection and disease. Three doses of P24-VP8* (200 μg/dose) intramuscular vaccine with Al(OH)3 adjuvant (600 μg) conferred significant protection against infection and diarrhea after challenge with virulent Wa strain rotavirus. This was indicated by the significant reduction in the mean duration of diarrhea, virus shedding in feces, and significantly lower fecal cumulative consistency scores in post-challenge day (PCD) 1–7 among vaccinated pigs compared to the mock immunized controls. The P24-VP8* vaccine was highly immunogenic in Gn pigs. It induced strong VP8*-specific serum IgG and Wa-specific virus-neutralizing antibody responses from post-inoculation day 21 to PCD 7, but did not induce serum or intestinal IgA antibody responses or a strong effector T cell response, which are consistent with the immunization route, the adjuvant used, and the nature of the non-replicating vaccine. The findings are highly translatable and thus will facilitate clinical trials of the P24-VP8* nanoparticle vaccine.

scholarly journals Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Anna Schorcht ◽  
Tom L. G. M. van den Kerkhof ◽  
Christopher A. Cottrell ◽  
Joel D. Allen ◽  
Jonathan L. Torres ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Vaccine Design ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Tier 2 ◽  
Broadly Neutralizing Antibodies ◽  
Subtype B ◽  
Hiv 1

ABSTRACT The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, can inform vaccine design by providing blueprints for the induction of similar bNAb responses. We describe a new recombinant native-like envelope glycoprotein (Env) SOSIP trimer, termed AMC009, based on the viral founder sequences of an elite neutralizer. The subtype B AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bNAb epitopes. Overall, its structure at 4.3-Å resolution was similar to that of BG505 SOSIP.664. The AMC009 trimer resembled one from a second elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, the AMC009 trimers did not induce autologous neutralizing antibody (NAb) responses efficiently while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the NAb activity from the rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers. These results advance our understanding of how to use Env trimers in multivalent vaccination regimens and the immunogenicity of trimers derived from elite neutralizers. IMPORTANCE Elite neutralizers, i.e., individuals who developed unusually broad and potent neutralizing antibody responses, might serve as blueprints for HIV-1 vaccine design. Here, we studied the immunogenicity of native-like recombinant envelope glycoprotein (Env) trimers based on viral sequences from elite neutralizers. While immunization with single trimers from elite neutralization did not recapitulate the breadth and potency of neutralization observed in these infected individuals, a combination of three subtype B Env trimers from elite neutralizers resulted in some neutralization breadth within subtype B viruses. These results should guide future efforts to design vaccines to induce broadly neutralizing antibodies.

scholarly journals BNT162b2 boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19

2021 ◽  
Author(s):  
Georg Behrens ◽  
Joana Barros-Martins ◽  
Anne Cossmann ◽  
Gema Morillas Ramos ◽  
Metodi Stankov ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Large Scale ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Protection ◽  
Cell Immunity ◽  
The Impact ◽  
As Effects

Abstract Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity, and large scale second booster vaccination is ongoing. However, data comparing declining immunity after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. We longitudinally monitored immunity in ChAd/ChAd (n=41) and ChAd/BNT (n=88) vaccinated individuals and assessed the impact of a second booster with BNT in both groups. The second booster greatly augmented waning anti-spike IgG but only moderately increased spike-specific CD4+ and CD8+ T cells in both groups to cell frequencies already present after the boost. More importantly, the second booster efficiently restored neutralizing antibody responses against Alpha, Beta, Gamma, and Delta, but neutralizing activity against B.1.1.529 (Omicron) stayed severely impaired. Our data suggest that inferior SARS-CoV-2 specific immune responses after homologous ChAd/ChAd vaccination can be cured by a heterologous BNT vaccination. However, prior heterologous ChAd/BNT vaccination provides no additional benefit for spike-specific T cell immunity or neutralizing Omicron after the second boost.

scholarly journals Studies of the Neutralizing Activity and Avidity of Anti-Human Immunodeficiency Virus Type 1 Env Antibody Elicited by DNA Priming and Protein Boosting

1998 ◽  
Vol 72 (11) ◽  
pp. 9092-9100 ◽  
Author(s):  
J. F. L. Richmond ◽  
S. Lu ◽  
J. C. Santoro ◽  
J. Weng ◽  
Shiu-Lok Hu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralizing Activity ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.

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