Persistence of Rabies Virus-Neutralizing Antibodies after Vaccination of Rural Population following Vampire Bat Rabies Outbreak in Brazil

Abstract

BackgroundAnimal control measures in Latin America have decreased the incidence of urban human rabies transmitted by dogs and cats; currently most cases of human rabies are transmitted by bats. In 2004–2005, rabies outbreaks in populations living in rural Brazil prompted widespread vaccination of exposed and at-risk populations. More than 3,500 inhabitants of Augusto Correa (Pará State) received either post-exposure (PEP) or pre-exposure (PrEP) prophylaxis. This study evaluated the persistence of rabies virus-neutralizing antibodies (RVNA) annually for 4 years post-vaccination. The aim was to evaluate the impact of rabies PrEP and PEP in a population at risk living in a rural setting to help improve management of vampire bat exposure and provide additional data on the need for booster vaccination against rabies.Methodology/Principal FindingsThis prospective study was conducted in 2007 through 2009 in a population previously vaccinated in 2005; study participants were followed-up annually. An RVNA titer >0.5 International Units (IU)/mL was chosen as the threshold of seroconversion. Participants with titers ≤0.5 IU/mL or Equivalent Units (EU)/mL at enrollment or at subsequent annual visits received booster doses of purified Vero cell rabies vaccine (PVRV). Adherence of the participants from this Amazonian community to the study protocol was excellent, with 428 of the 509 (84%) who attended the first interview in 2007 returning for the final visit in 2009. The long-term RVNA persistence was good, with 85–88.0% of the non-boosted participants evaluated at each yearly follow-up visit remaining seroconverted. Similar RVNA persistence profiles were observed in participants originally given PEP or PrEP in 2005, and the GMT of the study population remained >1 IU/mL 4 years after vaccination. At the end of the study, 51 subjects (11.9% of the interviewed population) had received at least one dose of booster since their vaccination in 2005.Conclusions/SignificanceThis study and the events preceding it underscore the need for the health authorities in rabies enzootic countries to decide on the best strategies and timing for the introduction of routine rabies PrEP vaccination in affected areas.

Systematic Booster after Rabies Pre-Exposure Prophylaxis to Alleviate Rabies Antibody Monitoring in Individuals at Risk of Occupational Exposure

“…Inadequate antibody titers were independently associated with male sex at birth in the present study. This result is consistent with the findings of several other studies that reported higher antibody titers after rabies PrEP or postexposure prophylaxis in females [ 11 , 12 , 14 , 15 ]. A stronger postvaccination antibody response in females has been evidenced with other vaccines such as hepatitis A, hepatitis B, rubella, diphtheria, tetanus, and brucella [ 16 ], whereas the response was stronger in males for other vaccines such as pneumococcal, meningococcal vaccines, measles, and yellow fever.…”

“…Several authors have shown that both higher seroconversion rates and higher antibody titers were observed in younger age groups [ 15 , 19 , 20 ]. However, no statistical association between age at PrEP and immune response was evidenced in our study.…”

“…Serology results using the ELISA method, however, are comparable to those of the RFFIT method. Moreover, ELISA is considered to be a reliable alternative when RFFIT is unavailable [ 6 , 13 , 15 , 23 ]. Several studies on antibody response to rabies vaccination in individuals with potential occupational exposure have been performed using an ELISA test [ 10 , 12 ], and most people vaccinated for occupational purposes worldwide have rabies antibody titration monitoring assessed using this method.…”

Factors influencing the immune response after a double-dose 2-visit pre-exposure rabies intradermal vaccination schedule: A retrospective study

“…Because of the limited number of female subjects, there was little statistical power to detect gender-related association. While other authors also found no relation between age or gender and immune response [10], some have reported gender-and age-related differences in seroconversion rates, GMTs and RVNA persistence in rabies 3 1 ID and 2 2 ID pre-exposure schedules [11,12,14,20,21]. Females were found to have higher antibody levels than males after a 2 2 ID [11] and after a 3 1 ID PrEP schedule [14].…”

Jumping species—a mechanism for coronavirus persistence and survival

“…Finally, enteric infection represents a significantly different tissue than the respiratory tract in terms of disease and adaptive immunity; thus, virus tropism differences between species and tissues may also contribute to limiting disease in bats. Similarly, while recent work has shown intact elements of adaptive immunity in bat species [ 17 , 18 , 19 ], the enteric location may generate a dampened adaptive response that permits viral maintenance similar to the members of the microbiome in humans [ 20 ]. Together, these factors likely work in combination and indicate how diverse pools of CoV quasi-species can survive in bat populations.…”