XBB.1.5, XBB.1.16, and XBB.2.3 were generated in the lab through site-directed mutagenesis via PCR. to SIV-negative dams. Additionally, SIV positive dams that received antiretroviral therapy experienced lower nAb titers than untreated dams. Our study underscores the importance of reformulating the COVID-19 vaccine to better protect against newly emerged XBB subvariants as well as the need for further investigation of vaccine effectiveness in individuals living with HIV-1. Keywords:SARS-CoV-2, neutralizing antibody, SIV, rhesus macaque, mRNA vaccination == Intro == The Omicron sublineage of SARS-CoV-2 offers displayed increasing extents of escape of neutralizing antibodies (nAb) stimulated by mRNA vaccination that persists Emodin even with fresh bivalent formulations17. Administration of the 3-dose mRNA vaccine can cause immune imprinting, resulting in reduced nAb titers against Omicron subvariants8,9. Bivalent vaccination can alleviate this reduction but only to a limited degree, especially against the newer XBB-lineage subvariants810. The disease burden of COVID-19 offers affected Emodin some populations more than others. One group are individuals living with HIV-111. People with advanced and/or untreated HIV-1 infection do not mount as effective as an immune response upon mRNA vaccination compared to treated counterparts12. Luckily, individuals receiving antiretroviral therapies (ART) do not look like at as high a risk for severe disease13,14. Currently, knowledge related to effectiveness of mRNA vaccination against SARS-CoV-2 in individuals living with HIV-1 remains limited. == Results == With this study, we investigated the nAb response inside a cohort of rhesus macaques including 10 dams (n=10) and 9 babies (n=9) (Fig. 1A,Furniture 1and2). Among the dams, seven were intravenously infected with SIV during the 1st trimester. Of these 7, three received ART during the early third trimester while the remaining four were untreated; ART was interrupted for over one year during the priming with the COVID vaccine (Table 2). Notably, none of the babies given birth to to SIV-infected dams tested positive for SIV (Table 2). All monkeys received two photos of Pfizer bivalent mRNA vaccine, which includes both WT and BA.4/5 spikes. An initial dose was given (day time 0) and a booster dose was administered 8 weeks after. Sera were collected at weeks 4, 8, and 10 after the Emodin 1st dose (Fig. 1B). Sera were used in a pseudotyped lentivirus neutralization assay15to determine the nAb response against XBB.1.5, XBB.1.16, and XBB.2.3 variant spikes alongside parental D614G and BA.4/5. == Number 1. Study design. == (A)Schematic depiction of cohorts explained with this study.(B)Timeline of vaccine administrations and blood sample selections. == Table 1: Summary of Rhesus Macaque Cohort. == Details of the macaque cohort are explained in the table. SIV nave dams were never exposed to SIV, and SIV nave babies were given birth to to uninfected dam cohorts. Babies given birth to to SIV-infected dams were tested as SIV bad. == Table 2: == SIV Status, SIV Titers, and frequencies of peripheral CD20+ B- and CD4+ T-Cells in the Macaque Cohort. These furniture provide details for the dam and infant portions of the macaque cohort, including the animal identification quantity (ANML ID), color coded by SIV status (green = nave; orange = SIV infected without ART; blue = SIV infected with ART), plasma viral weight (PVL) at time of the first vaccine dose, the percentage of CD20+ B cells (gated lymphocytes) and CD4+ T cells (gated CD3+ T cells) in peripheral blood samples using circulation cytometry at time of priming, as well Mouse monoclonal to PRKDC as the neutralizing antibody titers against D614G pseudovirus in the week 10 blood collection sample. Similar to humans16, we recognized nAb titers against D614G and Emodin BA.4/5 at week 4 after the first bivalent dose; titers declined at 8 weeks, but improved after improving at week 10 (Fig. 2A). Titers against XBB variants were near the limit of detection (NT50=40) throughout 8 weeks after the 1st dose, but their levels dramatically improved after improving, with D614G and BA.4/5 showing a 17~45 and 96~112-fold increase, respectively (Fig. 2A). The higher titer for BA.4/5 compared to D614G was in sharp contrast to what is seen humans, where, upon receiving 3 doses of monovalent vaccine and 1 dose of bivalent containing BA.4/5 spike, BA.4/5 titers are usually notably lower than D614G and titers against XBB variants often near-undetectable1,47. These findings spotlight that administration of bivalent vaccine only can generate strong nAb titers against Omicron subvariants. == Number 2. Neutralizing antibody response against SARS-CoV-2 spike in SIV-infected rhesus macaques and effect of age, SIV status, and ART treatment. == (A)The neutralizing antibody titers (NT50) for the full cohort against each of the SARS-CoV-2 variants separated by timepoint post-first vaccine dose (weeks 4, 8, and 10) are plotted.(B-C)The cohort is split into the dam titers(B)(n=10) and the infant titers(C)(n=9). For those panels, titers are offered as geometric means with 95%.