Immunogenicity of JN.1- and KP.2-Encoding mRNA COVID-19 Vaccines Against JN.1 Subvariants in Adult Participants

Immunogenicity of JN.1- and KP.2-Encoding mRNA COVID-19 Vaccines Against JN.1 Subvariants in Adult Participants | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Immunogenicity of JN.1- and KP.2-Encoding mRNA COVID-19 Vaccines Against JN.1 Subvariants in Adult Participants Amparo L. Figueroa , Bethany Girard , Darin K Edwards , Arshan Nasir , Kimball Johnson , Steven Hack , Xin Cao , Elizabeth de Windt , Veronica Urdaneta , Frances Priddy , Rituparna Das , David C Montefiori , Spyros Chalkias doi: https://doi.org/10.1101/2025.05.02.25325954 Amparo L. Figueroa 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: amparo.figueroa{at}modernatx.com Bethany Girard 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Darin K Edwards 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Arshan Nasir 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kimball Johnson 2 CenExel , Decatur, Georgia 30030, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Steven Hack 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xin Cao 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Elizabeth de Windt 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Veronica Urdaneta 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Frances Priddy 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rituparna Das 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site David C Montefiori 3 Duke University Medical Center , Durham, North Carolina 27710, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Spyros Chalkias 1 Moderna, Inc. , Cambridge, Massachusetts 02142, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF Abstract In this ongoing, open-label phase 3b/4 study, JN.1- and KP.2-encoding monovalent mRNA-1273 vaccines elicited robust neutralizing antibody responses against vaccine-matched variants and cross-neutralized currently circulating JN.1 subvariants (KP.3.1.1, XEC, LP.8.1) in adults with previous COVID-19 mRNA vaccination, with reduced cross-neutralization observed against all subvariants tested. No safety concerns were identified. Background Rapid spread and diversification of the SARS-CoV-2 Omicron lineage led to the JN.1 variant, which became globally dominant by early 2024 [ 1 ] and continues to diversify, with KP.2 having circulated previously, and KP.3.1.1, XEC, and LP.8.1 currently circulating worldwide [ 2 ]. XEC, a recombination-derived lineage [ 3 , 4 ] has acquired 2 new mutations (T22N, F59S), compared with the previously dominant KP.3 [ 3 , 5 ]. Recently, XEC is increasingly outcompeted by LP.8.1, a KP.1.1.3 subvariant containing 9 new spike mutations versus JN.1 [ 4 , 5 ] and 6 versus KP.2 [ 2 ]. LP.8.1 is increasingly prevalent globally, having become dominant in the United States [ 4 , 6 ]. While LP.8.1 seems to be no more immune-evasive than XEC, it shows enhanced spike-hACE2 engagement, likely facilitating its gradual replacement over XEC [ 5 ]. Due to increasing global prevalence, both have been classified as variants under monitoring by the World Health Organization [ 2 ], accounting for 76% of sequenced variants (LP.8.1: 70%; XEC: 6%) in the US as of May 2025 [ 6 ]. Antigenic evolution within the JN.1 lineage led to authorization of monovalent JN.1- and KP.2-encoding mRNA COVID-19 vaccines (2024-2025 formula) [ 7 , 8 ]. Preclinical versions of these vaccines evaluated in naive (2-dose primary series) and previously immunized mice (booster) were shown to neutralize vaccine-matched variants and cross-neutralize JN.1 subvariants KP.2, KP.3, LA.2, and XEC (XEC in naïve mice only) [ 9 ], supporting variant selection and updated vaccine approvals. The JN.1- and KP.2-encoding mRNA-1273 vaccines are expected to remain cross- reactive to emerging JN.1 lineage variants [ 4 , 9 ]; however, clinical data on potential cross-neutralization are not yet available. This study was conducted as part of an ongoing trial ( NCT06585241 ) aiming to generate human serology data to assess immunogenicity and cross-neutralization of updated variant formulations of mRNA-1273 as new SARS-CoV-2 variants emerge. We evaluated the immunogenicity and cross-neutralization of the JN.1- encoding vaccine (mRNA-1273.167) and the KP.2-encoding vaccine (mRNA-1273.712) against vaccine-matched variants and currently circulating variants (KP.3.1.1, XEC, LP.8.1) [ 2 , 6 ] in adults with previous COVID-19 mRNA vaccination; safety was also evaluated. Methods Study Design and Participants This is an ongoing, open-label, single-arm, phase 3b/4 study evaluating immunogenicity and safety of monovalent formulations of mRNA-1273 encoding the SARS-CoV-2 Omicron variants JN.1 (mRNA-1273.167) and KP.2 (mRNA-1273.712). Eligible participants were US adults (≥18 years) with ≥3 previous mRNA COVID-19 vaccinations (≥2 mRNA COVID-19 vaccines and an XBB.1.5-encoding mRNA COVID-19 vaccine received between September 2023-August 2024). Participants received a 0.5-mL dose of a single intramuscular injection (50 µg) of either mRNA-1273.167 (Subprotocol 1) or mRNA-1273.712 (Subprotocol 2) and were followed for 1 month. Adults with known history of SARS-CoV-2 infection within 3 months before enrollment were excluded ( Supplementary Appendix ). The study is being conducted in accordance with the Declaration of Helsinki and Council for International Organizations of Medical Sciences international ethical guidelines, International Council for Harmonisation good clinical practice guidelines, and applicable laws and regulations. Patient Consent Statement Protocol, informed consent form, and other relevant documents were reviewed and approved by the institutional review board/independent ethics committee (Advarra, Columbia, MD, USA) before study initiation. Informed consent was obtained prior to enrollment into the study. Study Vaccines mRNA-1273.167 (Spikevax, Moderna, Inc.) contains 50 µg of mRNA encoding the full-length SARS-CoV-2 spike protein of the JN.1 variant with 2 proline residue substitutions to stabilize the spike protein into a prefusion conformation. mRNA-1273.712 contains 50 µg of mRNA encoding the prefusion-stabilized spike protein of the KP.2 variant. Immunogenicity and Safety Assessments Sera for assessments of neutralizing antibody (nAb) responses were collected before vaccine administration (Day 1) and 4 weeks after immunization (Day 29). The nAb titers were quantified using a lentivirus-based SARS-CoV-2 pseudovirus neutralization assay (Duke University), described previously [ 10 ]. Safety assessments included adverse events (AEs) leading to study withdrawal, serious AEs (SAEs), and AEs of special interest (AESIs) from Day 1 through the end of the study. Statistical Analysis Immunogenicity was evaluated in the per-protocol immunogenicity set (PPIS), comprising all participants who received a planned study vaccine, had a negative reverse transcriptase polymerase chain reaction (RT-PCR) test at Days 1 and 29, and no major protocol deviations impacting the key data. The primary endpoint was geometric mean (GM) titer and GM fold rise (GMFR) of nAb at Day 29 relative to baseline, with corresponding 95% confidence intervals. Safety was assessed in the safety set (all enrolled participants who received study intervention). No statistical hypothesis testing was performed; a descriptive summary of the primary immunogenicity objective was provided. Results Overall, 50 participants were independently enrolled in each subprotocol and received mRNA-1273.167 (Subprotocol 1; median age, 63 years; 62% female; 86% Black/African American) or mRNA-1273.712 (Subprotocol 2; median age, 54 years; 66% female; 70% Black/African American). Median time on study was 30 days (mRNA-1273.167 cohort) and 29 days (mRNA-1273.712 cohort). Prior COVID-19 vaccination was categorized into 2, 3, 4, and ≥5 doses, with 76-80% of participants having received 3 doses across subprotocols (median time [interquartile range, IQR] since last dose: mRNA-1273.167, 310 days [303-316]; mRNA-1273.712, 330 days [277-338]). Prior COVID-19 vaccination included an original mRNA monovalent formulation (mRNA-1273 or BNT162b2: 100% recipients [mRNA-1273.167]; 96% recipients [mRNA-1273.712]), and Omicron bivalent formulation (mRNA-1273 or BNT162b2: 100% recipients [both subprotocols]). Baseline SARS-CoV-2 status was determined by virologic (RT-PCR) and/or serologic (anti-nucleocapsid binding antibody) evidence of SARS-CoV-2 infection on/before Day 1. No participants reported a known SARS-CoV-2 infection within the past 3 months. In Subprotocol 1, 39 (78.0%) participants were SARS-CoV-2 positive at baseline; PPIS included 48 (96.0%) participants (two were excluded due to a missing or positive SARS CoV-2 RT-PCR result on Day 29). In Subprotocol 2, 43 (86.0%) participants were baseline SARS-CoV-2 positive; PPIS included 49 (98.0%) participants (one was excluded due to a positive or missing SARS CoV-2 RT-PCR result on Day 29). Both JN.1-encoding (mRNA-1273.167) and KP.2-encoding (mRNA-1273.712) vaccines elicited robust increases in nAb responses at Day 29 relative to baseline against matched variants (GMFR, 11.6-11.7) and cross-neutralized JN.1-lineage subvariants not matched to the vaccine (GMFR, mRNA-1273.167: KP.2, 8.1; KP.3.1.1, 10.5; XEC, 12.9; LP.8.1, 10.8; GMFR, mRNA-1273.712: JN.1, 10.8; KP.3.1.1, 12.4; XEC, 12.1; LP.8.1, 14.3; Figure 1 ). The highest titers were measured against JN.1 for both vaccines (GMT: mRNA-1273.167, 1670.0; mRNA-1273.712, 2796.4). Relative to the JN.1 reference, a reduction in cross-neutralization was observed against JN.1-lineage subvariants (KP.3.1.1, XEC, LP.8.1) for both vaccines, with the greatest reduction measured against KP.3.1.1 ( Figure 2 ). Higher nAb responses were elicited by mRNA-1273.712 than mRNA-1273.167 against all tested variants ( Figure 2 ). Download figure Open in new tab Figure 1. Neutralizing antibody responses (GMT and GMFR) elicited by mRNA- 1273.167 (JN.1-encoding vaccine) and mRNA-1273.712 (KP.2-encoding vaccine) against the vaccine-matched variants (JN.1, KP.2) and newly emerged subvariants (KP.3.1.1, XEC, LP.8.1), per-protocol immunogenicity set. The GMT (Day 1 and Day 29) with the corresponding GMFR (Day 29 relative to Day 1) are shown. The per-protocol immunogenicity set included participants who received the planned study intervention, had negative RT-PCR tests at baseline (Day 1) 1) and Day 29, and had no major protocol deviations that impacted the key data. The boundary of boxes represents the 25th (bottom) and 75th (top) percentiles of the GMT. The solid line inside the box represents the median (50th percentile) of the GMT. The dashed line inside the box represents the GMT. Whiskers (vertical lines) represent the lowest and highest data points within 1.5 of the interquartile range. The LLOQ is presented using a grey dashed line. The LOD is presented using a brown dashed line. Abbreviations: GMFR, geometric mean fold rise; GMT, geometric mean titer; ID50, 50% inhibitory dilution; LLOQ, lower limit of quantification; LOD, limit of detection; RT-PCR, reverse transcription polymerase chain reaction. Download figure Open in new tab Figure 2. Geometric mean fold-drop in variant-specific neutralizing antibody responses at Day 29 after mRNA-1273.167 (JN.1-encoding vaccine) and mRNA- 1273.712 (KP.2-encoding vaccine), per-protocol immunogenicity set. The LLOQ is presented using a grey dashed line. The LOD is presented using a brown dashed line. Annotated fold change indicates fold-drop compared with the reference variant JN.1. Abbreviations: LLOQ, lower limit of quantification; LOD, limit of detection. No SAEs, deaths, or AEs leading to study withdrawal were reported throughout the study. One AESI (pulmonary embolism) was reported in the study, which was considered unrelated to vaccination by the investigator. At 23 days post-vaccination in the JN.1 cohort, a participant in their 50s with hypothyroidism presented to the emergency department with chest pain/diaphoresis; a small pulmonary embolism was found, and the participant was treated with anticoagulants and then discharged on oral anticoagulants. Discussion In this phase 3b/4 study evaluating adults with previous COVID-19 mRNA vaccination, monovalent JN.1-and KP.2-encoding mRNA-1273 vaccines (mRNA-1273.167, mRNA-1273.712) induced robust nAb responses against matched variants and cross-neutralized newly-emerged JN.1 subvariants (KP.3.1.1, XEC, LP.8.1). Cross-neutralization was reduced across all subvariants versus JN.1. No safety concerns were identified over the 1-month follow-up period. While both vaccines induced cross-neutralization consistent with the expected potent cross-reactivity of the JN.1- and KP.2-encoding vaccines against emerging JN.1-lineage subvariants [ 4 , 9 ], decreased cross-neutralization measured against KP.3.1.1, XEC, and LP.8.1 for both vaccines suggested that recently emerged variants have developed some immune escape from responses induced by currently approved COVID-19 vaccine compositions. At Day 29, the KP.2-encoding vaccine (mRNA-1273.712) induced higher nAb responses than the JN.1-encoding vaccine (mRNA-1273.167) against all variants tested, suggesting an advantage in preventing escape. The highest reduction in cross-neutralization was observed for KP.3.1.1, consistent with data reporting increased resistance to serum neutralization of KP.3.1.1 versus XEC in KP.2 vaccine recipients [ 11 ]. The drop in cross-neutralization versus the JN.1 reference ranged between 1.5 and 3.4 after the JN.1- and KP.2-encoding vaccines, which was lower than that reported against JN.1 (∼5.8-fold reduction) after booster vaccination with the XBB.1.5-encoding mRNA-1273 vaccine authorized for the 2023-2024 season [ 10 ]. These data are consistent with the reported cross-neutralization of KP.2 monovalent boosters against JN.1 subvariants, including KP.3.1.1 and XEC, and with observations of reduced neutralization against these subvariants versus JN.1 or KP.2 [ 12 , 13 ]. Similar findings were reported for the JN.1-encoding mRNA booster among healthcare workers, with the highest neutralization measured against JN.1, and 1.9- and 2.9-fold lower titers measured against KP.3.1.1 and XEC, respectively [ 14 ]. Study limitations include small sample size and lack of durability assessments of nAb responses. Higher baseline titers in the KP.2 cohort might have influenced higher nAb titers and fold-rises at Day 29, although greater fold-rises for KP.2, KP.3.1.1, and LP.8.1 were observed in the KP.2 cohort despite higher baseline titers. Participant enrollment in the JN.1 and KP.2 vaccine arms was non-randomized, and comparisons should be made cautiously. In conclusion, the JN.1- and KP.2-encoding monovalent mRNA-1273 vaccines elicited robust nAb responses against matched variants and cross-neutralized currently circulating JN.1 subvariants (KP.3.1.1, XEC, LP.8.1), with reduced cross-neutralization observed against all subvariants tested. No safety concerns were identified. Data Availability As the trial is ongoing, access to patient-level data presented in the article and supporting clinical documents by qualified external researchers who provide methodologically sound scientific proposals may be available upon reasonable request for products or indications that have been approved by regulators in the relevant markets and subject to review from 24 months after study completion. Such requests can be made to Moderna, Inc., 325 Binney Street, Cambridge, MA, 02142 USA <>. A materials transfer and/or data access agreement with the sponsor will be required for accessing shared data. All other relevant data are presented in the paper. Funding The work was supported by Moderna, Inc. Author contributions A.L.F., B.G., D.K.E., A.N., S.H., X.C., E.d.W., V.U., F.P., R.D., and S.C. conceived and planned the study. A.L.F., B.G., A.N., K.J., S.H., E.d.W., V.U., R.D., and D.C.M. collected the data. A.L.F., B.G., D.K.E., A.N., S.H., X.C., E.d.W., V.U., R.D., D.C.M., and S.C. contributed to data analysis and interpretation. All authors contributed to drafting of the manuscript and contributed to the critical revision of the manuscript for important intellectual content. All authors met the authorship criteria and approved the publication. Potential conflicts of interest A.L. F., B.G., D.K.E., A.N., S.H., X.C., E.D.W., V.U., F.P., R.D., and S.C., are employees of Moderna, Inc., and may hold stock/stock options in the company. K.J. is an employee of CenExel and holds stock in the company. D.C.M. reports laboratory funding from Moderna, Inc. Data availability statement As the trial is ongoing, access to patient-level data presented in the article and supporting clinical documents by qualified external researchers who provide methodologically sound scientific proposals may be available upon reasonable request for products or indications that have been approved by regulators in the relevant markets and subject to review from 24 months after study completion. Such requests can be made to Moderna, Inc., 325 Binney Street, Cambridge, MA, 02142 USA <>. A materials transfer and/or data access agreement with the sponsor will be required for accessing shared data. All other relevant data are presented in the paper. Figure Alt Text Figure 1: Graphs showing neutralizing antibody responses against vaccine-matched variants and newly emerged variants at baseline and Day 29 after JN.1- and KP.2- encoding mRNA-1273.712 vaccines, illustrated with boxplots and individual data points. Figure 2: Graphs comparing geometric mean fold-drop in variant-specific neutralizing antibody responses at Day 29 after JN.1- and KP.2-encoding mRNA- 1273.712 vaccines, illustrated with bars and individual data points. Acknowledgments Medical writing and editorial assistance were provided by Anja Varjačić, PhD, of MEDiSTRAVA in accordance with Good Publication Practice (GPP 2022) guidelines, funded by Moderna, Inc., and under the direction of the authors. These data were previously presented at the Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global), April 11-15, 2025, Vienna, Austria. Footnotes This revision includes additional details regarding an adverse event of special interest reported in the study, which was considered unrelated to vaccination by the investigator. References 1. ↵ World Health Organization . Updated Risk Evaluation of JN.1 09 February 2024 . Available at: https://cdn.who.int/media/docs/default-source/documents/health-topics/sars/jn.1-9-february-2024.pdf . Accessed December 12 2024 . 2. ↵ World Health Organization . WHO COVID-19 dashboard . Available at: https://data.who.int/dashboards/covid19/variants . Accessed May 19 2025 . 3. ↵ Kaku Y , Okumura K , Kawakubo S , et al. Virological characteristics of the SARS-CoV-2 XEC variant . Lancet Infect Dis 2024 ; 24 : e736 . OpenUrl CrossRef PubMed 4. ↵ World Health Organization. Initial Risk Evaluation of LP.8.1 03 February 2025 . Available at: https://www.who.int/publications/m/item/risk-evaluation-for-sars-cov-2-variant-under-monitoring-lp81 . Accessed March 4 2025 . 5. ↵ Liu J , Yu Y , Yang S , et al. Virological and antigenic characteristics of SARS-CoV-2 variants LF.7.2.1, NP.1, and LP.8.1 . Lancet Infect Dis 2025 ; 25 : e128 – 30 . OpenUrl PubMed 6. ↵ Centers for Disease Control and Prevention . COVID Data Tracker . Available at: https://covid.cdc.gov/covid-data-tracker/#variant-summary . Accessed May 19 2025 . 7. ↵ World Health Organization . Statement on the Antigen Composition of COVID-19 Vaccines . Available at: https://www.who.int/news/item/26-04-2024-statement-on-the-antigen-composition-of-covid-19-vaccines . Accessed March 4 2025 . 8. ↵ Food and Drug Administration . FDA Approves and Authorizes Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants . Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-and-authorizes-updated-mrna-covid-19-vaccines-better-protect-against-currently . Accessed March 4 2025 . 9. ↵ Lee DW , Nasir A , Elbashir S , et al. mRNA-1273 vaccines adapted to JN.1 or KP.2 elicit cross-neutralizing responses against the JN.1 sublineages of SARS-CoV-2 in mice . Vaccine 2025 ; 54 : 126961 . OpenUrl PubMed 10. ↵ Chalkias S , McGhee N , Whatley JL , et al. Interim Report of the Reactogenicity and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 XBB-Containing Vaccines . J Infect Dis 2024 ; 230 : e279 – 86 . OpenUrl CrossRef PubMed 11. ↵ Wang Q , Guo Y , Mellis IA , et al. Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC . bioRxiv 2024 :2024.11.17.624037. 12. ↵ Suthar MS , Manning KE , Ellis ML , et al. The KP.2-adapted COVID-19 vaccine improves neutralising activity against the XEC variant . Lancet Infect Dis 2025 ; 25 : e122 – 3 . OpenUrl PubMed 13. ↵ Wang Q , Mellis IA , Wu M , et al. KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2 . Lancet Infect Dis 2025 ; 25 : e133 – 4 . OpenUrl PubMed 14. ↵ Arora P , Happle C , Kempf A , et al. Impact of JN.1 booster vaccination on neutralisation of SARS-CoV-2 variants KP.3.1.1 and XEC . Lancet Infect Dis 2024 ; 24 : e732 – 3 . OpenUrl CrossRef PubMed View the discussion thread. Back to top Previous Next Posted June 04, 2025. 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Figueroa , Bethany Girard , Darin K Edwards , Arshan Nasir , Kimball Johnson , Steven Hack , Xin Cao , Elizabeth de Windt , Veronica Urdaneta , Frances Priddy , Rituparna Das , David C Montefiori , Spyros Chalkias medRxiv 2025.05.02.25325954; doi: https://doi.org/10.1101/2025.05.02.25325954 Share This Article: Copy Citation Tools Immunogenicity of JN.1- and KP.2-Encoding mRNA COVID-19 Vaccines Against JN.1 Subvariants in Adult Participants Amparo L. Figueroa , Bethany Girard , Darin K Edwards , Arshan Nasir , Kimball Johnson , Steven Hack , Xin Cao , Elizabeth de Windt , Veronica Urdaneta , Frances Priddy , Rituparna Das , David C Montefiori , Spyros Chalkias medRxiv 2025.05.02.25325954; doi: https://doi.org/10.1101/2025.05.02.25325954 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Infectious Diseases (except HIV/AIDS) Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (300) Cardiovascular Medicine (4435) Dentistry and Oral Medicine (444) Dermatology (382) Emergency Medicine (608) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1509) Epidemiology (15229) Forensic Medicine (30) Gastroenterology (1124) Genetic and Genomic Medicine (6600) Geriatric Medicine (668) Health Economics (997) Health Informatics (4536) Health Policy (1368) Health Systems and Quality Improvement (1613) Hematology (541) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15916) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (146) Nephrology (667) Neurology (6599) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1144) Occupational and Environmental Health (957) Oncology (3332) Ophthalmology (974) Orthopedics (369) Otolaryngology (420) Pain Medicine (436) Palliative Medicine (130) Pathology (663) Pediatrics (1693) Pharmacology and Therapeutics (691) Primary Care Research (711) Psychiatry and Clinical Psychology (5447) Public and Global Health (9232) Radiology and Imaging (2198) Rehabilitation Medicine and Physical Therapy (1370) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (712) Sports Medicine (530) Surgery (712) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a0089146ea97df94',t:'MTc3OTU4NjU2Ng=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();