The LP.8.1 variant of SARS-CoV-2, a descendant of the JN.1 lineage, has been spreading rapidly across the globe, exhibiting notable mutations in its spike protein. As of December 2024, the variant’s relative effective reproduction number (Re) is slightly higher than that of XEC, although transmission dynamics vary between countries such as the US and Japan. Despite showing 67% lower infectivity in pseudovirus assays compared to JN.1, LP.8.1's ability to spread is not fully understood. Mutations in its spike protein, including Ser31del and Phe186Leu, appear to increase infectivity, while others such as His445Arg and Phe456Leu reduce it. However, the infectivity of LP.8.1 remains lower than JN.1, yet similar to that of XEC.
In terms of immune resistance, neutralization assays conducted with sera from convalescent individuals and vaccine recipients revealed that LP.8.1 exhibits higher immune resistance compared to JN.1. Although, the resistance of LP.8.1 is similar to that of XEC and KP.3.1.1 across all serum groups tested. These results suggest that while LP.8.1 has lower pseudovirus infectivity than JN.1, its immune resistance is comparable to XEC and KP.3.1.1. Notably, differences in the immune landscape across various countries may influence LP.8.1’s spread, with varying immune backgrounds and vaccination histories playing a significant role. Further studies are necessary to fully understand the impact of LP.8.1 on global transmission and immune resistance.
In an email interview with Kei Sato, PhD, associate professor from the Division of Systems Virology, Department of Microbiology and Immunology at The Institute of Medical Science, The University of Tokyo, provided further insights into the factors driving the transmission and immune resistance of the LP.8.1 variant, as well as its spread across different countries.
According to Sato, the transmissibility of LP.8.1, like other SARS-CoV-2 variants, largely depends on the immune condition within different populations. He explained, “Currently, the transmissibility (we call it ‘relative reproduction number (Re)’ in our work) would mainly depend on the immune condition in the people. Viruses evolve to evade the (humoral) immunity in the host.” He further emphasized that the primary driver of immunity in many countries, particularly in early 2024, was the JN.1 variant. “Now it has been revealed that the immunity against SARS-CoV-2 variants could be ‘imprinted’. Now we have the 5-year history of COVID. Most people got vaccinated multiply (Wuhan-based, BA.1-based, BA.5-based, ...), and got infected certain variant possibly multiply. Therefore, the immunity in each country may differ. This may affect the difference of LP.8.1 spread in each country.”
What You Need To Know
The LP.8.1 variant has a mix of mutations in its spike protein that reduce its pseudovirus infectivity, but its actual transmission dynamics are not fully understood.
LP.8.1 shows higher immune resistance than JN.1, with variations in immune response across countries influenced by prior infections and vaccination history.
The spread of LP.8.1 is influenced by "imprinted" immunity shaped by previous infections and vaccinations, creating different immune profiles across populations.
Despite the lower pseudovirus infectivity of LP.8.1, the variant continues to spread globally. Sato acknowledged, “Yes this is the concern. Based on our data, we cannot fully explain the reason why LP.8.1 possibly outcompetes XEC in some countries.” He offers two possible explanations for this observation. “One possibility is explained above. The other may be that our pseudovirus infectivity does not necessarily reflect the full characteristic of LP.8.1; the effect of certain mutations in non-spike regions cannot be reflected in pseudovirus (because it only has spike). Therefore, it is possible that non-spike mutations can affect the viral characteristics of LP.8.1.” Sato suggests that mutations outside the spike protein may influence LP.8.1’s infectivity and its ability to spread, despite the lower infectivity observed in pseudovirus assays.
Additionally, Sato discussed how immune resistance in LP.8.1 reflects population immunity shaped by previous infections or vaccinations. He explained that immunity to SARS-CoV-2 can be “imprinted” by prior exposures to specific variants, whether through natural infection or vaccination. “As explained above, anti-SARS-CoV-2 immunity can be imprinted by the variant infected/vaccinated. In most countries, people got Wuhan-based vaccines and several variants spread. On the other hand, China did not use Wuhan-based vaccine (because of long-term national lockdown), then massively spread BA.5, meaning that Chinese have not been primed by Wuhan, but they primed BA.5. So immune background can be quite different.” This variation in immune profiles across countries may contribute to the differences in immune resistance observed in LP.8.1.
Sato’s insights underscore the complexity of viral evolution and immunity. The diverse immune backgrounds across populations, shaped by vaccination campaigns and prior infections, play a significant role in the spread and immune resistance of new variants like LP.8.1. To fully understand the global impact of these factors, further research and data from multiple countries are essential.
Reference
Chen L, Kaku Y, Okumura K, et al. Virological characteristics of the SARS-CoV-2 LP.8.1 variant. Lancet Infect Dis. February 10, 2025. February 13, 2024. doi:10.1016/S1473-3099(25)00079-9
