Impact of BRICS’ investment in vaccine development on the global vaccine market

Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.     

Effectiveness of the herpes zoster vaccine Zostavax® in Stockholm County,Sweden

ObjectiveThe objective of this study was to estimate the effectiveness of the herpes zoster vaccine Zostavax in a cohort of vaccinated individuals in Sweden.MethodsThe study is a retrospective population-based matched cohort study conducted with data from health care registers in Stockholm Country. Primary endpoints were new diagnosis of HZ after administration of Zostavax. Individuals above the age of 50 years and living in Stockholm County in 2013 were included into the study. Ten non-vaccinated individuals per vaccinated were included and randomized into the cohort. The non-vaccinated were matched on age at index date and gender.ResultsZostavax had an overall effectiveness (VE) of 34% (HR = 0.66, 95% CI: 0.55–0.78). When stratifying by age, 61–75 years was the only age group that showed a reduced risk of HZ (HR = 0.57; CI 0.44–0.73) compared to those that were non-vaccinated. As compared to the unvaccinated group, the VE was significant at days 180–359 (HR = 0.53; 95% CI 0.33–0.88), 360–539 (HR = 0.46; 95% CI 0.27–0.80) and at days 540–719 (HR = 0.56; 95% CI 0.35–0.90) after vaccination.ConclusionThis is the first population-based study in Sweden studying the effectiveness of HZ vaccination. Our findings are well in-line with previous studies, however studies addressing the longitudinal efficacy and effectiveness of Zostavax are still required.     

Seroprevalence of rubella antibodies in the State of São Paulo,Brazil, 8 years after the introduction of vaccine

Rubella vaccine was introduced in the official immunization calendar of the State of S?o Paulo, in 1992, at 15 months of age, following a mass vaccination targeting all children between 1 and 10 years of age. This mixed strategy was designed taking into account serological data and mathematical models to estimate the optimal ages for vaccination. To evaluate the efficacy of routine vaccination on rubella infection in S?o José do Rio Preto, State of S?o Paulo, 8 years after the introduction of vaccine, a seroprevalence survey was carried out in December 2000, comprising 1,536 subjects aging from 6 months to 25 years. Rubella specific IgG was detected in blood samples by enzyme-linked immunosorbent assay (ELISA). From 18 months to 5 years of age (covered by a mass vaccination campaign 6 months before the study) the seroprevalence was above 90%. From 6 to 8 years of age (vaccinated by routine schedule at 15 months), the seroprevalence was 76%. From 9 to 18 years of age (vaccinated at the mass campaign that introduced the vaccine 8 years before) the seroprevalence was about 85%. After 20 years of age, protection was acquired by previous infection, as they were not covered by any vaccine program. From 20 to 25 years of age, the seroprevalence was 70%. As the seroprevalence remains low at ages not vaccinated, it should be expected low infection rates at this age window. Despite this, the present situation deserves care, as routine vaccination is given a protection below the minimum level necessary (80%). The efficacy of the proposed strategy depends on better routine vaccination coverage. A second dose of vaccine should also be considered.     

Failure to vaccinate or failure of vaccine? Effectiveness of the 23-valent pneumococcal polysaccharide vaccine program in Indigenous adults in the Northern Territory of Australia

Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001–2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI −43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.     

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013–18

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.MethodsVE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.ResultsIn the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505–0.621], 0.550 [95% CI, 0.516–0.586]), 0.549 [95% CI, 0.517–0.583], and 1.014 [95% CI, 0.907–1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.ConclusionsBoth one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.     

Monitoring the safety of high-dose,trivalent inactivated influenza vaccine in the vaccine adverse event reporting system (VAERS), 2011 – 2019

BackgroundOn 12/23/2009 a new high-dose trivalent inactivated influenza vaccine (IIV3-HD) was licensed for adults aged ≥65 years. We assessed the post-licensure safety data for IIV3-HD in the Vaccine Adverse Event Reporting System (VAERS) during 2011–2019.MethodsWe searched VAERS for reports after IIV3-HD during 1/1/2011–06/30/2019 in persons aged ≥65 years. Medical records were reviewed for all death reports and for certain pre-specified conditions (e.g. Guillain Barré Syndrome [GBS], anaphylaxis). We also reviewed certain groups who received IIV3-HD erroneously (e.g. pregnant women, children). Empirical Bayesian data mining was used to identify disproportional reporting.ResultsVAERS received 12,320 reports after IIV3-HD;723 reports (5.9%) were serious. The most common adverse events (AEs) among serious reports were pyrexia (30.2%), asthenia (28.9%), and dyspnea (24.9%), and among non-serious reports were injection site erythema (16.8%), pain in extremity (15.8%), and injection site pain (14.2%). Among 55 death reports, the most common causes of death were diseases of the circulatory system (n = 23;41.8%). Based on medical record review, there were 61 reports of GBS and 13 of anaphylaxis. There were 13 reports of pregnant-women who inadvertently received IIV3-HD; three reports described arm pain or local reactions, and 10 did not report any AE. Among 59 reports of children who erroneously received IIV3-HD, 31 experienced an AE (most commonly injection site or constitutional reactions) and the remaining 28 reports did not describe any AE.ConclusionsPost-licensure safety data of IIV3-HD during 9 influenza seasons revealed no new or unexpected safety concerns among individuals ≥65 years. Inadvertent administration of IIV3-HD to children or pregnant women was observed, although with no serious AEs reported. Training and education of providers in vaccine recommendations and groups for whom the vaccine is indicated may help in preventing these vaccine administration errors. This review provides baseline information for future monitoring of the quadrivalent-high-dose influenza vaccine.     

Empirically driven definitions of “good,” “moderate,” and “poor” levels of functioning in the treatment of schizophrenia

Purpose

This study used an empirical approach to identify and validate the classification of patients with schizophrenia in “good,” “moderate,” or “poor” functioning groups based on the assessment of functional measures.

Methods

Using data from a study of schizophrenia outpatients, patients were classified into functional groups using cluster analysis based on the Heinrich–Carpenter Quality of Life Scale (QLS), the 36-item Short-Form Health Survey (SF-36) Mental Component Summary Score, and a productivity measure. A three-cluster solution was chosen. Concurrent, convergent, and discriminant validity were assessed. Criteria for classifying patient functioning as “good,” “moderate,” or “poor” were established using classification and regression tree analysis.

Results

The three clusters consistently differentiated patients on the QLS, SF-36 Mental Component Summary Score, and productivity measure. The clusters also differed on other functional measures and were concordant with previous functional classifications. Concurrent, convergent, and discriminant validity were good. “Good” functioning was identified as a QLS total score ≥84.5; “moderate” and “poor” functioning were separated by a cutoff score of 15.5 on the QLS intrapsychic foundation domain. Sensitivity ranged from 86 to 93 % and specificity from 89 to 99 %.

Conclusions

The heterogeneity in functioning of schizophrenia patients can be classified reliably in an empirical manner using specific cutoff scores on commonly used functional measures.     

Trends in the uptake of pediatric measles-containing vaccine in the United States: A Disneyland effect?

BackgroundThe measles outbreak that began in December 2014 at the California Disneyland theme park in the United States (U.S.) received a high amount of media attention. Media attention can influence health-related behaviors. We investigated the effect of the Disneyland outbreak on measles-containing vaccine (MCV) uptake among U.S. children.MethodsWe used 2012–2017 National Immunization Survey-Child (NIS-Child) data to examine MCV uptake among U.S. children by 19 months of age. We classified MCV coverage among birth cohorts as exposed based on age at the time of the outbreak. A difference-in-differences design with adjustment for categorical birth cohort was implemented in base models to estimate the exposure effect on the outcomes, ≥1-dose MCV coverage or age at first MCV dose, with pneumococcal conjugate vaccination as a control. Primary analyses included this model adjusted for geographic region, maternal education, race/ethnicity, household income, and insurance status, and an exposure-interaction term with maternal education. All analyses included sampling weights.ResultsThe study population represented 34,471,357 children. In base models, the Disneyland outbreak was associated with a 1.0% (95% CI: 0.2%, 1.8%) increase in ≥1-dose MCV coverage and a 6.6 (95% CI: 4.8, 8.5)-day decrease in MCV administration age. In primary analyses, the outbreak was associated with a 3.9% (95% CI: 3.1%, 4.8%) increase in ≥1-dose MCV coverage among children of college-educated mothers, and a 3.2% (95% CI: 0.6%, 5.9%) decrease among children of mothers earning less than a high school degree. Decreases in MCV administration age ranging from 5.9 (95% CI: 3.3, 8.5) to 9.1 (95% CI: 6.8, 11.4) days were observed across maternal education categories.ConclusionsThe Disneyland outbreak was associated with differential effects on MCV coverage by maternal education and decreases in MCV administration age among U.S. children. These findings may provide useful insights to inform methods to address pediatric MCV undervaccination.     

Rapid identification of herd effects with the introduction of serogroup C meningococcal conjugate vaccine in Ontario,Canada, 2000–2006

In 2001, Canada's National Advisory Committee on Immunization endorsed a meningococcal serogroup C conjugate vaccine, which appears to provide durable serogroup-specific immunity while reducing nasopharyngeal carriage. With reference to direct and indirect effects on case occurrence, we sought to evaluate recent trends in the incidence of invasive meningococcal disease (IMD) in Ontario. Analyses included all IMD cases reported between 2000 and 2006 to the Ontario Central Public Health Laboratory. Poisson models incorporating terms for age, sex and seasonal oscillation identified a significant downward trend in disease occurrence, which was strongest in serogroup C cases and not evident when serogroup C strains were excluded from the analysis. Among age groups not targeted by the vaccine program serogroup C, IMD displayed a pattern of decreasing incidence that was not present in non-serogroup C disease. These apparent dramatic effects of conjugate C vaccine (both direct and indirect) may be important in the implementation and evaluation of vaccine policy in other jurisdictions.     

Immunogenicity of the AIK-C measles vaccine in infants aged <9 months in Vietnam

Measles-associated deaths have been reported in infants <9 months during outbreaks. A cohort study was conducted on 210 infants aged 6–8 months to evaluate the immunogenicity and safety of the AIK-C measles vaccine containing 10^4.21 plaque-forming units (PFU)/0.5 mL produced in Vietnam. Paired serum samples were obtained from 196 subjects. Seropositivity was defined as ≥120 mIU/mL. The seroresponse rate was 173/196 (88.27%, 95% confidence interval (CI): 83.77–92.77%) with geometric mean titer (GMT) of 511 mIU/mL (95% CI: 688–880 mIU/mL), and no significant differences were observed by different age groups. Among 196 paired sera, they were categorized into four groups: 122 subjects <14 IU/mL, 28 subjects 14–<60 mIU/mL, 30 subjects 60–<120 mIU/mL, and 16 subjects ≥ 120 mIU/mL. The seroresponse rate was 112/122 (91.8%, 95% CI: 86.94–96.67%) with GMT (597 mIU/mL, 95% CI: 749–1002 mIU/mL) in the <14 mIU/L group. In the 14–<60 mIU/mL group, the seroresponse rate was 18/28 (64.29%) with 184 mIU/L of GMT and was significantly lower (p < 0.01) than that in the <14 mIU/mL group. In the 16 seropositive group, all subjects showed seroconversion (4-fold higher than before) with a higher GMT of 1078 mIU/mL. Local pain and itching at the injection site were observed in 8 subjects (3.8%) within 7 days of the vaccination. Regarding systemic adverse reactions, febrile illness ≥37.5 °C was observed in 14 subjects (6.7%). These results indicate that the AIK-C measles vaccine is effective and safe for infants aged 6–8 months and will contribute to reducing the number of measles-associated deaths in future outbreaks.     

Evaluating the effectiveness of the influenza vaccine during respiratory outbreaks in Singapore’s long term care facilities, 2017

Influenza outbreaks occur periodically in Long Term Care Facilities (LTCFs) and vaccination is critical in preventing influenza infections. We evaluated the influenza vaccine effectiveness (VE) during respiratory outbreaks in LTCFs reported to the Ministry of Health, Singapore in 2017.A test-negative design was used to estimate the ratio of the odds of testing positive for influenza among vaccinated individuals to the odds among unvaccinated individuals. The VE was calculated as (1-odds ratio) × 100%. For adjusted VE, the estimates were derived using logistic regression adjusted for age group, gender, month of illness, and number of days from date of illness onset till to swab collection date. Estimates by influenza subtypes and post-vaccination time periods (15–180 days & 181–365 days) were also calculated using stratified data.264 individuals, with 118 laboratory-confirmed influenza cases [32 A(H1N1)pdm09, 75 A(H3N2), 11 A(untypable)], were included in the analysis. No one was identified to be infected with influenza B. The overall adjusted VE estimate was 40.5% (95% CI: −12.2–68.5%), while the subtype-specific adjusted VE estimates were −43.4% (95% CI: −312.4–50.2%) against A(H1N1)pdm09 and 57.1% (95% CI: 5.7–80.5%) against A(H3N2). At 15–180 days post-vaccination period, the adjusted VEs were 59.3% (95% CI: 18.0–79.8%) against all influenza, 35.4% (95% CI: −123.5–81.3%) against A(H1N1)pdm09 and 67.9% (95% CI: 22.5–86.7%) against A(H3N2). Estimates were not significant at 181–365 days post-vaccination.The influenza vaccine showed varying effectiveness among individuals in Singapore’s LTCFs in 2017, with a higher effectiveness among those who were more recently vaccinated. It remains an important tool in preventing influenza infections, especially for those who are at high risk of influenza-related complications.     

Epidemiology of invasive pneumococcal disease in the pre-conjugate vaccine era: South Africa, 2003–2008

Introduction

Dynamics of pneumococcal disease incidence and serotype distribution prior to introduction of pneumococcal conjugate vaccines (PCV) will assist in understanding effects of the vaccine over time and will be important in choosing the optimal PCV formulation.

Methods

We conducted active, laboratory-based, national surveillance for invasive pneumococcal disease (IPD) through the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) from 2003 through 2008. Over 130 laboratories report to this system. Pneumococci were serotyped using Quellung and isolates screened for resistance by disk diffusion; minimum inhibitory concentrations were determined on potentially resistant isolates. We used univariate and multivariable multinomial regression models to assess differences between serotypes.

Results

GERMS-SA identified 8674 cases among children <5 years. Overall, 58% (3849/6668), 65% (4314/6668), and 85% (5669/6668) of cases and 61% (455/751), 64% (482/751), 82% (616/751) of deaths were due to serotypes included in 7-valent PCV, 10-valent PCV and 13-valent PCV, respectively. Serotypes 6A and 19A accounted for 16% (527/3252) of penicillin non-susceptible disease. In 2008, reported incidence of IPD was 6-fold higher in children <1 compared to children 1–4 years of age: 87 per 100,000 population and 14/100,000, respectively. The relative risk of IPD was 21-fold (95% CI, 19–24) and 34-fold (29–41) greater in HIV-infected compared to HIV-uninfected children in the <1 year and 1–4-year-old age groups respectively. On multivariable analysis serotypes 6B (relative risk ratio (RRR) 0.7; confidence interval (CI) 0.5–0.9), 18C (RRR 0.3; CI 0.1–0.5), 1 (RRR 0.2; CI 0.1–0.4) and 8 (RRR 0.2; CI 0.1–0.4) were significantly less common in HIV-infected individuals than serotype 14.

Conclusions

All vaccine formulations have the potential to prevent most cases and deaths from IPD in children in South Africa. Vaccines with protection against 19A would be advantageous in South Africa.     

Estimation of oral poliovirus vaccine effectiveness in Afghanistan, 2010–2020

BackgroundAfghanistan is one of two countries with endemic wild poliovirus type 1 (WPV1). The oral poliovirus vaccine (OPV) is the predominant vaccine used for polio eradication. Although OPV has been administered in routine childhood immunization and during frequent supplementary immunization activities, WPV1 continues to circulate in Afghanistan and case incidence has been increasing since 2017. We estimated the effectiveness of OPV in Afghanistan during 2010–2020.MethodsWe conducted a matched case-control analysis using acute flaccid paralysis (AFP) surveillance data from 29,370 children < 15 years with AFP onset between January 1, 2010 and December 31, 2020. We matched children with confirmed WPV1 (cases) with children with non-polio AFP (controls) by age at onset of paralysis (+/- 3 months), date of onset of paralysis (+/- 3 months), and province of residence, and compared their reported OPV vaccination history to estimate the effectiveness of OPV in preventing paralysis by WPV1 using conditional logistic regression. To account for changes in OPV formulations provided over the analysis period, we stratified the analysis based on dates of the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) in April 2016.ResultsBetween January 1, 2010 and December 31, 2020, there were 329 WPV1 cases in Afghanistan. The per-dose estimated effectiveness of OPV against WPV1 was 19% (95% CI: 15%–22%) and of ≥ 7 doses was 94% (95% CI: 90%-97%). Before the global switch from tOPV to bOPV, the per-dose estimated effectiveness of OPV was 14% (95% CI: 11%-18%) and of ≥ 7 doses was 92% (95% CI: 85%-96%). After the switch, the per-dose estimated effectiveness of OPV against WPV1 was 32% (24%-39%) and of ≥ 7 doses was 96% (95% CI: 90%-99%).DiscussionOPV is highly effective in preventing paralysis by WPV1; these results indicate that continued WPV1 transmission in Afghanistan is due to failure to vaccinate, not failure of the vaccine. Although difficult to implement in parts of country, improving the administration of OPV in routine immunization and supplementary immunization activities will be critical for achieving polio eradication in Afghanistan.     

Modeling the durability of ZOSTAVAX® vaccine efficacy in people ≥60 years of age

Since 2006, the vaccine, ZOSTAVAX^®, has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.     

Is the adjuvanted influenza vaccine more effective than the trivalent inactivated vaccine in the elderly population? Results of a case–control study

Introduction

Influenza illness is an important public health problem and annual vaccination is globally recommended for high risk populations.

Objective

The aim was to evaluate and compare the effectiveness of influenza vaccines in reducing hospitalizations for influenza or pneumonia during two influenza seasons in the elderly.

Methods

A case–control study was performed, using administrative database of the Local Health Unit Roma-A (LHU RM-A). The included subjects were at least 65 years old and residing in one of the four districts of the LHU. The cases were hospitalized for influenza or pneumonia during influenza season in the years 2010–2011 and 2011–2012. The controls were hospitalized in the same period, but not for influenza or pneumonia. The subjects were immunized with the trivalent inactivated influenza vaccine (TIV) in the first influenza season (2010–2011) and with the adjuvanted influenza vaccine MF59 (ATIV) in the second season (2011–2012).

Results

A total of 269 cases and 1247 controls were included for the 2010–2011 influenza season, and 365 cases and 1227 controls were selected for the 2011–2012 season. Up to 63.6% cases and 53.5% controls in the 2010–2011 season and 78.6% of cases and 64.1% of controls in the 2011–2012 season have not been vaccinated. Female gender and high educational level were protective factors for hospitalization. Subjects over 75 years were at high risk of hospitalization compared to 65–74 years olds. Influenza vaccination reduced significantly hospitalization in both seasons. In subjects with 65–74 years TIV was more effective than ATIV; vice versa for those over 75 years old.

Discussion and conclusion

TIV and ATIV reduce hospitalization for influenza or pneumonia with a variable degree of protection in different age groups. In particular, ATIV is more effective in individuals over 75 years old.     

Evaluation of the safety profile of the vaccine candidate Brucella melitensis 16MΔvjbR strain in goats

Small ruminant brucellosis is caused by the Gram negative cocci-bacillus Brucella (B.) melitensis, the most virulent Brucella species for humans. In goats and sheep, middle to late-term gestation abortion, stillbirths and the delivery of weak infected offspring are the characteristic clinical signs of the disease. Vaccination with the currently available Rev. 1 vaccine is the best option to prevent and control the disease, although it is far from ideal. In this study, we investigate the safety of the B. melitensis 16MΔvjbR strain during a 15-month period beginning at vaccination of young goats, impregnation, delivery and lactation. Forty, 4 to 6 months old, healthy female crossbreed goats were randomly divided into four groups (n = 10) and immunized subcutaneously with a single vaccine dose containing 1x10⁹ CFU of B. melitensis 16MΔvjbR delivered in alginate microcapsules or non-encapsulated. Controls received empty capsules or the commercially available Rev.1 vaccine. Seven months post-vaccination, when animals were sexually mature, all goats were naturally bred using brucellosis-free males, and allowed to carry pregnancies to term. Blood samples to assess the humoral immune response were collected throughout the study. At two months post-delivery, all dams and their offspring were euthanized and a necropsy was performed to collect samples for bacteriology and histology. Interestingly, none of the animals that received the vaccine candidate regardless of the formulation exhibited any clinical signs associated with vaccination nor shed the vaccine strain through saliva, vagina or the milk. Gross and histopathologic changes in all nannies and offspring were unremarkable with no evidence of tissue colonization or vertical transmission to fetuses. Altogether, these data demonstrate that vaccination with the mutant strain 16MΔvjbR is safe for use in the non-pregnant primary host.