A study published in Science (2010) investigated the human antibody response to dengue virus (DENV), which has four serotypes. The research found that antibodies targeting the prM protein, a structural precursor-membrane protein of DENV, dominate the immune response. These antibodies are highly cross-reactive among the four DENV serotypes but do not neutralize the virus effectively. Instead, they promote antibody-dependent enhancement (ADE), increasing viral replication in Fc-receptor-bearing cells like monocytes and macrophages. DENV is a mosquito-borne virus found in tropical and subtropical regions, with an estimated 50-100 million infections annually. Infection with one serotype does not provide protection against others, leading to common secondary infections. ADE is a hypothesis for increased severity in secondary infections, where antibodies may enhance viral entry into cells. The study generated human monoclonal antibodies (mAbs) against DENV. Of the 3020 cell lines tested, 301 were positive, with 73% reacting to the whole virus and 27% to NS1. Western blot analysis showed that 78% of supernatants reacted to E or prM, with anti-prM antibodies being dominant. Anti-prM antibodies showed cross-reactivity among DENV serotypes but not with Japanese encephalitis virus (JEV), which is a related flavivirus. The study also found that anti-prM antibodies could not fully neutralize DENV, suggesting that the virus may exist in two populations: one susceptible to neutralization and another not. Partial cleavage of prM from the viral surface reduces antigen availability, making the virus susceptible to ADE by anti-prM. This finding has implications for vaccine design, as vaccines should aim to minimize the anti-prM response. The study used various methods, including ELISA, Western blot, and focus-forming assays, to analyze the immune response. It also tested the effect of prM cleavage on neutralization and enhancement, finding that viruses with high prM levels were less infectious but could be made infectious by ADE. The study concluded that anti-prM antibodies are a dominant component of the immune response to DENV, and their ability to promote ADE may be an immune evasion strategy of the virus. The findings suggest that future DENV vaccines should minimize the anti-prM response to reduce the risk of ADE.A study published in Science (2010) investigated the human antibody response to dengue virus (DENV), which has four serotypes. The research found that antibodies targeting the prM protein, a structural precursor-membrane protein of DENV, dominate the immune response. These antibodies are highly cross-reactive among the four DENV serotypes but do not neutralize the virus effectively. Instead, they promote antibody-dependent enhancement (ADE), increasing viral replication in Fc-receptor-bearing cells like monocytes and macrophages. DENV is a mosquito-borne virus found in tropical and subtropical regions, with an estimated 50-100 million infections annually. Infection with one serotype does not provide protection against others, leading to common secondary infections. ADE is a hypothesis for increased severity in secondary infections, where antibodies may enhance viral entry into cells. The study generated human monoclonal antibodies (mAbs) against DENV. Of the 3020 cell lines tested, 301 were positive, with 73% reacting to the whole virus and 27% to NS1. Western blot analysis showed that 78% of supernatants reacted to E or prM, with anti-prM antibodies being dominant. Anti-prM antibodies showed cross-reactivity among DENV serotypes but not with Japanese encephalitis virus (JEV), which is a related flavivirus. The study also found that anti-prM antibodies could not fully neutralize DENV, suggesting that the virus may exist in two populations: one susceptible to neutralization and another not. Partial cleavage of prM from the viral surface reduces antigen availability, making the virus susceptible to ADE by anti-prM. This finding has implications for vaccine design, as vaccines should aim to minimize the anti-prM response. The study used various methods, including ELISA, Western blot, and focus-forming assays, to analyze the immune response. It also tested the effect of prM cleavage on neutralization and enhancement, finding that viruses with high prM levels were less infectious but could be made infectious by ADE. The study concluded that anti-prM antibodies are a dominant component of the immune response to DENV, and their ability to promote ADE may be an immune evasion strategy of the virus. The findings suggest that future DENV vaccines should minimize the anti-prM response to reduce the risk of ADE.