Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection

Engdahl, Taylor B.; Kuzmina, Natalia; Ronk, Adam J.; Mire, Chad E.; Hyde, Matthew A.; Kose, Nurgun; Josleyn, Matthew; Sutton, Rachel E.; Mehta, Apoorva; Wolters, Rachael M.; Lloyd, Nicole M.; Valdivieso, Francisca; Ksiazek, Thomas G.; Hooper, Jay W.; Bukreyev, Alexander; Crowe, James E.

doi:10.1016/j.celrep.2021.109453

Cited by 4 publications

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“…6A). This dose was demonstrated to be uniformly lethal in our previous studies 10,71 . The control animals started showing abrupt disease signs on 9 dpc (lack of movement and reactions to experimenter, hunched posture, rapid shallow breathes) and were euthanized within 24 h with progressive severe respiratory distress.…”

Section: M1ψ Modi Cation Of Mrna Does Not Signi Cantly Affect the Tra...mentioning

confidence: 73%

“…While the m1Ψ modi cation of mRNA prevents the effective innate immune response, its effect on the translation is marginal We evaluated the expression of Gn/Gc in A549 cells at 24 h post transfection with either U-mRNA or m1Ψ-mRNA in equal concentrations by ow cytometry using a cocktail of human monoclonal antibodies that are capable to bind ANDV Gn/Gc antigen and neutralize ANDV in vivo 10 , with FITC-labeled secondary antibody. The results demonstrated effective expression of the antigen in cells transfected with either construct (Fig.…”

Section: Design Of the Andv Gpc Mrna Vaccine Constructmentioning

confidence: 99%

“…Further, the cleaved Gn and Gc form heterodimer Gn/Gc complexes on the virion surface that interact with host cell receptors and trigger receptor-mediated endocytosis and further pH-driven membrane fusion via conformational changes of Gc 8, 9 . It was shown that monoclonal antibodies directed to Gn or Gc of ANDV can e ciently neutralize the virus 10 . Orthohantavirus N is conserved, and viruses from various species demonstrate antigenic cross-reactivity based on the N 11,12 .…”

Section: Introductionmentioning

confidence: 99%

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Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Bukreyev

Kuzmin

Acosta

et al. 2023

Preprint

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Andes virus (ANDV) is a rodent-borne zoonotic orthohantavirus endemic in South America that causes hantavirus pulmonary syndrome in humans, with up to a 40% case fatality rate. We developed ANDV mRNA vaccines based on the M segment of the viral genome that codes for glycoproteins Gn and Gc in a single open reading frame of glycoprotein precursor (GPC). We generated RNAs either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Mice immunized by either ANDV U-mRNA or m1Ψ-mRNA developed similar germinal center responses in lymph nodes. Single cell RNA and BCR sequencing of germinal center B cells from vaccinated mice demonstrated similar levels of activation, except an additional cluster of cells exhibiting strong interferon response that was present in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Furthermore, similar immunoglobulin class-switching and somatic hypermutations were observed for the two vaccines. Golden Syrian hamsters were immunized intramuscularly with 2 doses of the vaccines on days 0 and 21. The titers of Gn/Gc-binding antibodies were moderately greater for U-mRNA construct than for m1Ψ-mRNA construct, however, the titers of ANDV-neutralizing antibodies were equivalent. Vaccinated animals were challenged with a lethal dose of ANDV at 21 days after the boost, along with the naïve control group. All control animals succumbed to infection whereas all vaccinated animals survived without any detectable disease or viral load. The data demonstrate the development of effective vaccines against ANDV and the lack of a significant effect of m1Ψ mRNA modification on immunogenicity and protection in the hamster model.

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Section: M1ψ Modi Cation Of Mrna Does Not Signi Cantly Affect the Tra...mentioning

confidence: 73%

Section: Design Of the Andv Gpc Mrna Vaccine Constructmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Bukreyev

Kuzmin

Acosta

et al. 2023

Preprint

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“…This phenomenon often contributes to the differences in magnitude and longevity of the humoral response to natural infections, in comparison with vaccines [ 4 ]. Despite recent advancements in the characterization of monoclonal antibody responses to a number of human pathogens, including human immunodeficiency virus 1 [ 5 ], influenza virus [ 6 ], dengue virus [ 7 ], chikungunya virus [ 8 ], rabies virus [ 9 ], paramyxoviruses [ 10 ], poxviruses [ 11 ], hantaviruses [ 12 ], filoviruses [ 13 ], and coronaviruses [ 14 ], critical knowledge gaps still exist. In particular, many viral and host factors that determine the dynamics of antibody response and their role in pathogenesis, as well as the mechanisms of antiviral and proviral antibody effects, remain undefined.…”

mentioning

confidence: 99%