Cross-neutralizing antibody titres against non-vaccine types induced by a recombinant trivalent HPV vaccine (16/18/58) in rhesus macaques

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

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

Veterinární Medicína ◽

10.17221/7886-vetmed ◽

2001 ◽

Vol 46 (No. 9–10) ◽

pp. 241-243 ◽

Cited By ~ 1

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 Clostridium perfringens beta and epsilon toxoids induced protective humoral immune responses in buffalos. Total of 24 buffalos were divided into 4 groups (n = 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 < 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.

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Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope

Journal of Virology ◽

10.1128/jvi.01221-14 ◽

2015 ◽

Vol 89 (16) ◽

pp. 8130-8151 ◽

Cited By ~ 18

Author(s):

Katie M. Kilgore ◽

Megan K. Murphy ◽

Samantha L. Burton ◽

Katherine S. Wetzel ◽

S. Abigail Smith ◽

...

Keyword(s):

Simian Immunodeficiency Virus ◽

Nonhuman Primate ◽

Neutralizing Antibodies ◽

Rhesus Macaques ◽

Neutralizing Antibody ◽

Cd40 Ligand ◽

Antibody Activity ◽

Immunodeficiency Virus ◽

Antibody Profile ◽

Hiv 1

ABSTRACTAntibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (HIV-1) vaccine. To this end, preclinical simian immunodeficiency virus (SIV)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. However, these trials often rely on a limited selection of SIV strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. To mirror the viral panels used to assess HIV-1 antibody breadth, we created and characterized a novel panel of 14 genetically and phenotypically diverse SIVsm envelope (Env) glycoproteins. To assess the utility of this panel, we characterized the neutralizing activity elicited by four SIVmac239 envelope-expressing DNA/modified vaccinia virus Ankara vector- and protein-based vaccination regimens that included the immunomodulatory adjuvants granulocyte-macrophage colony-stimulating factor, Toll-like receptor (TLR) ligands, and CD40 ligand. The SIVsm Env panel exhibited a spectrum of neutralization sensitivity to SIV-infected plasma pools and monoclonal antibodies, allowing categorization into three tiers. Pooled sera from 91 rhesus macaques immunized in the four trials consistently neutralized only the highly sensitive tier 1a SIVsm Envs, regardless of the immunization regimen. The inability of vaccine-mediated antibodies to neutralize the moderately resistant tier 1b and tier 2 SIVsm Envs defined here suggests that those antibodies were directed toward epitopes that are not accessible on most SIVsm Envs. To achieve a broader and more effective neutralization profile in preclinical vaccine studies that is relevant to known features of HIV-1 neutralization, more emphasis should be placed on optimizing the Env immunogen, as the neutralization profile achieved by the addition of adjuvants does not appear to supersede the neutralizing antibody profile determined by the immunogen.IMPORTANCEMany in the HIV/AIDS vaccine field believe that the ability to elicit broadly neutralizing antibodies capable of blocking genetically diverse HIV-1 variants is a critical component of a protective vaccine. Various SIV-based nonhuman primate vaccine studies have investigated ways to improve antibody-mediated protection against a heterologous SIV challenge, including administering adjuvants that might stimulate a greater neutralization breadth. Using a novel SIV neutralization panel and samples from four rhesus macaque vaccine trials designed for cross comparison, we show that different regimens expressing the same SIV envelope immunogen consistently elicit antibodies that neutralize only the very sensitive tier 1a SIV variants. The results argue that the neutralizing antibody profile elicited by a vaccine is primarily determined by the envelope immunogen and is not substantially broadened by including adjuvants, resulting in the conclusion that the envelope immunogen itself should be the primary consideration in efforts to elicit antibodies with greater neutralization breadth.

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The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody

PLoS ONE ◽

10.1371/journal.pone.0253487 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253487

Author(s):

Conrad E. Z. Chan ◽

Shirley G. K. Seah ◽

De Hoe Chye ◽

Shane Massey ◽

Maricela Torres ◽

...

Keyword(s):

Therapeutic Efficacy ◽

Neutralizing Antibodies ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Rhesus Macaques ◽

Neutralizing Antibody ◽

Effector Functions ◽

Viral Loads ◽

Therapeutic Doses ◽

Dose Dependent

Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development of SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from a convalescent patient. Antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the SARS-CoV-2 Spike protein. SC31 exhibited potent anti-SARS-CoV-2 activities in multiple animal models. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, treatment with SC31 greatly reduced viral loads and attenuated pro-inflammatory responses linked to the severity of COVID-19. Importantly, a comparison of the efficacies of SC31 and its Fc-null LALA variant revealed that the optimal therapeutic efficacy of SC31 requires Fc-mediated effector functions that promote IFNγ-driven anti-viral immune responses, in addition to its neutralization ability. A dose-dependent efficacy of SC31 was observed down to 5mg/kg when administered before viral-induced lung inflammatory responses. In addition, antibody-dependent enhancement was not observed even when infected mice were treated with SC31 at sub-therapeutic doses. In SARS-CoV-2-infected hamsters, SC31 treatment significantly prevented weight loss, reduced viral loads, and attenuated the histopathology of the lungs. In rhesus macaques, the therapeutic potential of SC31 was evidenced through the reduction of viral loads in both upper and lower respiratory tracts to undetectable levels. Together, the results of our preclinical studies demonstrated the therapeutic efficacy of SC31 in three different models and its potential as a COVID-19 therapeutic candidate.

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Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (GL): induction of virus-neutralizing antibody and assessment of protection in ponies

Journal of General Virology ◽

10.1099/0022-1317-82-10-2425 ◽

2001 ◽

Vol 82 (10) ◽

pp. 2425-2435 ◽

Cited By ~ 17

Author(s):

J. Castillo-Olivares ◽

A. A. F. de Vries ◽

M. J. B. Raamsman ◽

P. J. M. Rottier ◽

K. Lakhani ◽

...

Keyword(s):

Envelope Glycoprotein ◽

Neutralizing Antibody ◽

Equine Arteritis Virus ◽

Post Vaccination ◽

Degree Of Protection ◽

Glycoprotein G ◽

Virus Excretion ◽

Unvaccinated Control ◽

Antibody Titres ◽

Immunization Study

An Escherichia coli-expressed recombinant protein (6hisGLecto) comprising the entire ectodomain (aa 18–122) of equine arteritis virus (EAV) glycoprotein GL, the immunodominant viral antigen, induced higher neutralizing antibody titres than other GL-derived polypeptides when compared in an immunization study in ponies. The potential of the recombinant GL ectodomain to act as a sub-unit vaccine against EAV was evaluated further in three groups of four ponies vaccinated with doses of 35, 70 or 140 μg of protein. All vaccinated animals developed a virus-neutralizing antibody (VNAb) response with peak titres 1–2 weeks after the administration of a booster on week 5 (VNAb titres of 1·8–3·1), 13 (VNAb titres of 1·4–2·9) or 53 (VNAb titres of 1·2–2·3). Vaccinated and unvaccinated control ponies were infected with EAV at different times post-vaccination to obtain information about the degree of protection relative to the levels of pre-challenge VNAb. Vaccination conferred varying levels of protection, as indicated by reduced or absent pyrexia, viraemia and virus excretion from the nasopharynx. The degree of protection correlated well with the levels of pre-challenge VNAb and, in particular, with levels of virus excretion. These results provide the first evidence that a sub-unit vaccine protects horses against EAV. The use of the sub-unit vaccine in combination with a differential diagnostic test based on other EAV antigens would enable serological discrimination between naturally infected and vaccinated equines.

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Attempts to infect pigs with Coxsackie virus type B5

Journal of Hygiene ◽

10.1017/s0022172400023871 ◽

1974 ◽

Vol 73 (1) ◽

pp. 85-96 ◽

Cited By ~ 11

Author(s):

A. J. M. Garland ◽

J. A. Mann

Keyword(s):

Virus Type ◽

Neutralizing Antibody ◽

Coxsackie Virus ◽

Virus Population ◽

Serological Relationship ◽

Anamnestic Response ◽

Transient Rise ◽

Buccal Swabs ◽

Antibody Titres ◽

Vesicular Disease

SUMMARYDespite the existence of a close serological relationship between the entero-viruses Swine Vesicular Disease (SVD) and Coxsackie type B5 (Cx B5), the administration of this Coxsackie virus type to susceptible pigs by various routes failed to produce clinical disease.Viraemia was not detected after exposure but virus was recovered intermittently from faeces and buccal swabs. A mixed virus population was demonstrated in faecal cultures from some pigs, including Coxsackie virus type B5 and other agents, presumably native pig enteroviruses. The Coxsackie virus persisted in faeces in declining amounts for up to 8 days after primary exposure.Serum neutralizing antibody showed a transient rise to Coxsackie virus, reaching a peak at 14 days and declining below demonstrable titres by 28 days after exposure. The antibody titres attained were proportional to the dose of virus administered and the degree of neutralization was very similar to both SVD and Cx B5 viruses.On cross challenge by exposure to SVD virus 28 days after exposure to Cx B5 virus, most animals (5/6) succumbed with typical vesicular lesions, although the serum neutralizing antibody titres showed a characteristically anamnestic response to both viruses.

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Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

npj Vaccines ◽

10.1038/s41541-020-00252-w ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Maria Blasi ◽

Donatella Negri ◽

Kevin O. Saunders ◽

Erich J. Baker ◽

Hannah Stadtler ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Lentiviral Vector ◽

Rhesus Macaques ◽

Infected Individual ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Safety And Efficacy ◽

Env Protein ◽

Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms.

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Human enterovirus infection in stray dogs. Some aspects of interest to public health

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651996000200012 ◽

1996 ◽

Vol 38 (2) ◽

pp. 157-161 ◽

Cited By ~ 3

Author(s):

Eliseu Alves Waldman ◽

Regina C. Moreira ◽

Sueli G. Saez ◽

Denise F.C. Souza ◽

Rita de C.C. Carmona ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Human Enterovirus ◽

Poliovirus Type ◽

Stray Dogs ◽

Wild Poliovirus ◽

Antibody Titres ◽

Global Eradication ◽

Type 3 ◽

Echovirus Type

To investigate the possible role of domestic animals as reservoirs of human enteroviruses, we studied 212 stray dogs captured in different areas of the municipality of São Paulo. The captured animals were divided into 19 groups of 10 to 20 dogs each; faeces of 126 of the 212 dogs were processed for enterovirus isolation. The following viruses were isolated from 12 dogs: poliovirus type 1 (2 dogs), poliovirus type 3 (1 dog), echovirus type 7 (8 dogs) and echovirus type 15 (1 dog). Of the 12 infected animals, four had specific homotypic neutralizing antibody titres > 16. All 212 animals were tested for the presence of neutralizing antibodies to human enteroviruses. The frequency of neutralizing antibodies present in titres of > 16 was 10.3%, 3,8% and 4.3% for vaccinal prototypes of polioviruses 1, 2 and 3 respectively; 1,9%, 1.4% and 1.5% for wild prototypes of the same viruses, 11.3% for echovirus 7, and 2.4% for echovirus 15. The proportion of dogs with neutralizing antibodies varied with the virus studied. Some indication of the susceptibility of dogs to infection with human enteroviruses was demonstrated, and the importance of this fact for the Plan for Global Eradication of the Wild Poliovirus is discussed.

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Trends in Poliovirus Seroprevalence in Kano State, Northern Nigeria

Clinical Infectious Diseases ◽

10.1093/cid/ciy637 ◽

2018 ◽

Vol 67 (suppl_1) ◽

pp. S103-S109

Author(s):

Harish Verma ◽

Zubairu Iliyasu ◽

Kehinde T Craig ◽

Natalie A Molodecky ◽

Utibeabasi Urua ◽

...

Keyword(s):

Old Age ◽

Age Groups ◽

Significant Risk ◽

Immunization Coverage ◽

Neutralizing Antibody ◽

Age Group ◽

Parental Consent ◽

Population Immunity ◽

Antibody Titres ◽

The Impact

Abstract Background Kano state has been a protracted reservoir of poliovirus in Nigeria. Immunity trends have been monitored through seroprevalence surveys since 2011. The survey in 2015 was, in addition, intended to assess the impact of use of inactivated poliovirus vaccine (IPV). Methods It was a health facility based seroprevalence survey. Eligible children aged 6-9, 12-15 and 19-22 months of age brought to the paediatrics outpatient department of Murtala Mohammad Specialist Hospital between 19 October and 6 November 2015, were screened for eligibility. Eligible children were enrolled after parental consent, history taken, physical examination conducted, and a blood sample collected to test for neutralizing antibody titres against the three poliovirus serotypes. Results Overall, 365 results were available in the three age groups. In the 6-9-month-old age group, the seroprevalence was 73% (95% confidence interval [CI] 64-80%), 83% (95% CI 75-88%), and 66% (95% CI 57-73%) for serotypes 1, 2, and 3, respectively. In the 12-15- and 19-22-month-old age groups, seroprevalence was higher but still remained <90% across serotypes. Seroprevalence to serotypes 1 and 3 in 2015 was similar to 2014; however, for serotype 2 there was a significant improvement. IPV received in supplemental immunization activities was found to be a significant predictor of seropositivity among 6-9-month-old infants for serotypes 1 and 2. Conclusions Seroprevalence for serotypes 1 and 3 remains low (<80%) in 6-9-month-olds. This poses a significant risk for poliovirus spread if reintroduced into the population. Efforts to strengthen immunization coverage are imperative to secure and sustain high population immunity.

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