Analysis of Zika virus neutralizing antibodies in normal healthy Thais (original) (raw)

Zika virus (ZIKV) infections have been reported from all over Thailand, but the number of reported cases remains low, suggesting a degree of immune protection against ZIKV infection. To address this possibility, the presence of ZIKV neutralizing antibodies was determined in serum from 135 healthy Thai adults with a plaque reduction neutralization test (PRNT), and a number of samples were subsequently analyzed for the presence of neutralizing antibodies to dengue virus (DENV) and Japanese encephalitis virus (JEV). Results showed that 70.4% (PRNT 50 ≥ 10), 55.6 (PRNT 50 ≥ 20) or 22.2% (PRNT 90 ≥ 20) of the samples showed neutralizing antibodies to ZIKV. Detailed analysis showed no association between the presence of neutralizing antibodies to other flaviviruses (DENV, JEV) and the presence of ZIKV neutralizing antibodies. These results suggest that the level of ZIKV neutralizing antibodies in the Thai population is enough to dampen the transmission of the virus in Thailand. ZIKV was first isolated from a sentinel monkey in Zika forest Uganda in 1947 1 , and the virus was isolated from Aedes africanus mosquitoes in the same forest a year later 1. The first reported human case of ZIKV infection was reported nearly a decade later, with infection again occurring in Zika forest in Uganda 2,3. Between the initial identification of ZIKV and 2007 only a few sporadic cases of human ZIKV infection in Africa and Asia were reported (as reviewed elsewhere 4). In 2007 a small outbreak on the islands of Yap State in Micronesia represented the first time the virus was detected outside of Africa and Asia and analysis suggested this virus has originated in Southeast Asia 5. The virus again emerged from Southeast Asia in 2013 where it was detected as the causative agent in an outbreak of Zika fever in French Polynesia 6. The virus subsequently spread to many of the islands in the Pacific Ocean, and was detected in Brazil in March 2015 7,8 , and within one year more than a million cases of infection were reported. From Brazil the virus spread quickly to other countries in South, Central and North America (as reviewed elsewhere 4). While serological studies have suggested the presence of ZIKV in Southeast Asia for more than 60 years 9-11 , definitive evidence of the presence of the virus was first reported in 1966 12 , and the first virologically confirmed case of human infection was reported from Cambodia in 2010 13. In 2013 two tourists to Thailand were diagnosed on their return to their home countries with ZIKV infection 14,15 and a subsequent retrospective study by the Thai Ministry of Health confirmed that the virus was present in Thailand and causing disease in the local population 16 , with the earliest confirmed cases dating to infections occurring in 2012. Currently, some 1,600 cases of ZIKV infection are reported to have occurred in 2016 and 2017 by the Thai Ministry of Public Health 17. The basis of the markedly different population impact of ZIKV in the Americas and Southeast Asia remains unknown. At least three human pathogenic mosquito transmitted flavivirus circulate in Thailand, and in addition to ZIKV, both dengue virus (DENV) and Japanese encephalitis virus (JEV) circulate. DENV consists of four closely related, but antigenically distinct viruses 18 , termed DENV 1 to 4 all of which are endemic in Thailand 19. Currently the main public health problem caused by these viruses is infections with DENV, as there are an average of 50,000 cases per year in Thailand, and DENV infection is the leading cause of hospitalization amongst children in Southeast Asia 20. There is a national vaccination program to protect against JEV infections established in 1990 21 , however, JEV infection was the leading cause of hospitalizations for encephalitis in a study undertaken between 2003 and 2005 22. DENV infection induces protective immunity that lasts for many decades and possibly lifelong 23. However the immunity raised is against the homotypic virus only, and only limited or transient protection is generated against heterotypic DENV, and thus multiple infections with DENV are possible 24. Studies have shown that some 90% of Thai adults have antibodies against at least one DENV 25-27. Given the national JEV vaccination campaign, adults