A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

Rompay, Koen K. A. Van; Coffey, Lark L.; Kapoor, Tania; Gazumyan, Anna; Keesler, Rebekah I.; Jurado, Andrea; Agudelo, Marianna; Watanabe, Jennifer; Usachenko, Jodie; Singapuri, Anil; Immareddy, Ramya; Ardeshir, Amir; Stuart, Jackson B.; Bournazos, Stylianos; Ravetch, Jeffrey V.; Balderes, Paul; Lorenz, Ivo C.; Esswein, Shannon R.; Keeffe, Jennifer R.; Björkman, Pamela J.; Wang, Qiao; Rice, Charles M.; MacDonald, Margaret R.; Nussenzweig, Michel C.; Robbiani, Davide F.

doi:10.1073/pnas.2000414117

Cited by 25 publications

(17 citation statements)

References 55 publications

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“…can be modified to prevent interactions with the Fc gamma receptor and that remain protective against viral pathogens 23 .…”

Section: Articlementioning

confidence: 99%

“…These interactions can enhance immunity and help clear the pathogen or infected cells, but they can also lead to disease enhancement during Dengue 20 and possibly coronavirus infections 21 . This problem has impeded Dengue vaccine development but would not interfere with the clinical use of potent neutralizing antibodies that can be modified to prevent Fc gamma receptor interactions and remain protective against viral pathogens 22 .…”

mentioning

confidence: 99%

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Convergent antibody responses to SARS-CoV-2 in convalescent individuals

Robbiani

Gaebler

Muecksch

et al. 2020

Nature

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1,889

265

2,651

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During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2 1-5. Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC 50 values) as low as 2 ng ml −1. In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

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“…can be modified to prevent interactions with the Fc gamma receptor and that remain protective against viral pathogens 23 .…”

Section: Articlementioning

confidence: 99%

mentioning

confidence: 99%

Convergent antibody responses to SARS-CoV-2 in convalescent individuals

Robbiani

Gaebler

Muecksch

et al. 2020

Nature

Self Cite

1,889

265

2,651

View full text Add to dashboard Cite

show abstract

“…These interactions can enhance immunity and help clear the pathogen or infected cells, but they can also lead to disease enhancement during Dengue 13 and possibly coronavirus infections 14 . This problem has impeded Dengue vaccine development but would not interfere with the clinical use of potent neutralizing antibodies that can be modified to prevent Fc gamma receptor interactions and remain protective against viral pathogens 15 .…”

mentioning

confidence: 99%

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

Robbiani

Gaebler

Muecksch

et al. 2020

Preprint

Self Cite

132

199

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During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain(RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2 1-5 . Here we report on 68 COVID-19 convalescent individuals. Plasmas collected an average of 30 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 18% to below 1:1000 in 78%, while only 3% showed titers >1:5000. Antibody cloning revealed expanded clones of RBDspecific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as few ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 without hospitalization do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

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“…Here, we sought to extend our VLP vaccine development studies to include the rhesus macaque model. Rhesus macaques have been used as models of ZIKV disease and also as vaccine efficacy [ 56 , 63 – 67 ]. In regard to our NHP ZIKV challenge studies, it was demonstrated that only 3 of 5 alum only immunized control NHP animals demonstrated infection detectable by plaque assay.…”

Section: Discussionmentioning

confidence: 99%

Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus

et al. 2021

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Background Zika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV. Methodology/Principle findings We have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge. Conclusions/Significance These studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials.

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A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

Cited by 25 publications

References 55 publications

Convergent antibody responses to SARS-CoV-2 in convalescent individuals

Convergent antibody responses to SARS-CoV-2 in convalescent individuals

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus

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