tetano
Editor, Senior Moderator
J Virol
. 2026 Aug 26:e0074926.
doi: 10.1128/jvi.00749-26. Online ahead of print.
Sanjeev Kumar 1 2 , Lilin Lai 1 2 3 , Madison L Ellis 1 2 3 , Anamika Patel 4 , Devyani Joshi 1 2 , Jacob W Vander Velden 1 2 3 , Jana Ziad Abu Faraj 5 , Sonia T Wimalasena 5 , Ramitha R Pallavi 5 , Jad Iriss 5 , Kareem Bechnak 5 , Peter Cook 6 , Meredith E Gardner 6 , Heather N Hicks 6 , Azaibi Tamin 6 , Clint Paden 6 , Jennifer L Harcourt 6 , Sri Edupuganti 2 7 , Nadine Rouphael 2 5 7 , Eric A Ortlund 4 , Alberto Moreno 2 3 7 , Vineet D Menachery 1 2 , Veronika I Zarnitsyna 8 , Jens Wrammert 1 2 , Mehul S Suthar 1 2 3 8
Affiliations
The emergence of the SARS-CoV-2 Omicron BA.2.86 subvariant, a lineage derived from the BA.2 strain, led to the 2024-2025 COVID-19 vaccine update to include KP.2 or related JN.1-lineage spike antigens. We evaluated the magnitude, breadth, and durability of humoral immune responses following a single KP.2 vaccine dose in a longitudinal cohort of 21 individuals up to 6 months. KP.2 vaccination increased spike-specific binding and neutralizing antibodies against the ancestral WA.1 strain, as well as against the BA.5, XBB.1.5, and KP.2 variants. Power-law modeling estimated half-lives for WA.1- and KP.2-specific IgG responses at 770 and 248 days, respectively. Additionally, the KP.2 dose increased IgG1 and IgG4 subclasses more than IgG2 and IgG3 responses to both spike proteins. Serum-depletion experiments using WA.1 or KP.2 proteins demonstrated that most vaccine-elicited antibodies were cross-reactive. Consequently, KP.2 vaccine-induced antibodies retained broad neutralizing activity against recently circulating Omicron subvariants (BA.2.86, KP.3.1.1, XEC, LP.8.1, LF.7, XFG.3.12, PQ.1, BA.3.2.1, and RE.2). Using a live virus neutralization assay, XFG.3.12 showed the greatest reduction in neutralizing titers relative to KP.2 (4.2-fold). In a small subset, an LP.8.1 vaccine dose increased neutralizing activity against the matched variant while maintaining WA.1 and KP.2 cross-reactivity, but only modestly increased antibodies to divergent variants BA.3.2.1 and RE.2. Ultimately, these data indicate the KP.2 mRNA vaccine generates durable, cross-reactive responses against current Omicron subvariants. However, ongoing spike evolution impacts the neutralization of emerging lineages, highlighting the need for continued viral monitoring and timely vaccine updates.
Importance: SARS-CoV-2 continues to evolve, raising ongoing concerns about how well updated vaccines protect against emerging variants. This study evaluates antibody responses after a KP.2 spike mRNA vaccine dose. It shows that a single dose induces durable and broadly cross-reactive immunity against both earlier strains and recently circulating Omicron subvariants. Despite this breadth, reduced neutralizing activity against certain emerging variants indicates that ongoing antigenic changes can impact vaccine-induced antibody effectiveness. These findings provide insight into how current vaccines perform over time and highlight the need to track viral evolution and update vaccine antigens to maintain broad protection against severe disease, hospitalization, and death.
Keywords: COVID-19; SARS-CoV-2; SARS-CoV-2 variants; antibody responses; humoral immunity; vaccine.
. 2026 Aug 26:e0074926.
doi: 10.1128/jvi.00749-26. Online ahead of print.
Immunological imprinting shapes the cross-reactive antibody responses to the KP.2 and LP.8.1 vaccine doses
Sanjeev Kumar 1 2 , Lilin Lai 1 2 3 , Madison L Ellis 1 2 3 , Anamika Patel 4 , Devyani Joshi 1 2 , Jacob W Vander Velden 1 2 3 , Jana Ziad Abu Faraj 5 , Sonia T Wimalasena 5 , Ramitha R Pallavi 5 , Jad Iriss 5 , Kareem Bechnak 5 , Peter Cook 6 , Meredith E Gardner 6 , Heather N Hicks 6 , Azaibi Tamin 6 , Clint Paden 6 , Jennifer L Harcourt 6 , Sri Edupuganti 2 7 , Nadine Rouphael 2 5 7 , Eric A Ortlund 4 , Alberto Moreno 2 3 7 , Vineet D Menachery 1 2 , Veronika I Zarnitsyna 8 , Jens Wrammert 1 2 , Mehul S Suthar 1 2 3 8
Affiliations
- PMID: 42644605
- DOI: 10.1128/jvi.00749-26
Abstract
The emergence of the SARS-CoV-2 Omicron BA.2.86 subvariant, a lineage derived from the BA.2 strain, led to the 2024-2025 COVID-19 vaccine update to include KP.2 or related JN.1-lineage spike antigens. We evaluated the magnitude, breadth, and durability of humoral immune responses following a single KP.2 vaccine dose in a longitudinal cohort of 21 individuals up to 6 months. KP.2 vaccination increased spike-specific binding and neutralizing antibodies against the ancestral WA.1 strain, as well as against the BA.5, XBB.1.5, and KP.2 variants. Power-law modeling estimated half-lives for WA.1- and KP.2-specific IgG responses at 770 and 248 days, respectively. Additionally, the KP.2 dose increased IgG1 and IgG4 subclasses more than IgG2 and IgG3 responses to both spike proteins. Serum-depletion experiments using WA.1 or KP.2 proteins demonstrated that most vaccine-elicited antibodies were cross-reactive. Consequently, KP.2 vaccine-induced antibodies retained broad neutralizing activity against recently circulating Omicron subvariants (BA.2.86, KP.3.1.1, XEC, LP.8.1, LF.7, XFG.3.12, PQ.1, BA.3.2.1, and RE.2). Using a live virus neutralization assay, XFG.3.12 showed the greatest reduction in neutralizing titers relative to KP.2 (4.2-fold). In a small subset, an LP.8.1 vaccine dose increased neutralizing activity against the matched variant while maintaining WA.1 and KP.2 cross-reactivity, but only modestly increased antibodies to divergent variants BA.3.2.1 and RE.2. Ultimately, these data indicate the KP.2 mRNA vaccine generates durable, cross-reactive responses against current Omicron subvariants. However, ongoing spike evolution impacts the neutralization of emerging lineages, highlighting the need for continued viral monitoring and timely vaccine updates.
Importance: SARS-CoV-2 continues to evolve, raising ongoing concerns about how well updated vaccines protect against emerging variants. This study evaluates antibody responses after a KP.2 spike mRNA vaccine dose. It shows that a single dose induces durable and broadly cross-reactive immunity against both earlier strains and recently circulating Omicron subvariants. Despite this breadth, reduced neutralizing activity against certain emerging variants indicates that ongoing antigenic changes can impact vaccine-induced antibody effectiveness. These findings provide insight into how current vaccines perform over time and highlight the need to track viral evolution and update vaccine antigens to maintain broad protection against severe disease, hospitalization, and death.
Keywords: COVID-19; SARS-CoV-2; SARS-CoV-2 variants; antibody responses; humoral immunity; vaccine.