Rubella virus neutralizing antibody response after a third dose of measles-mumps-rubella vaccine in young adults

BackgroundThird doses of measles-mumps-rubella (MMR) vaccine have been administered during mumps outbreaks and in various non-outbreak settings. The immunogenicity of the rubella component has not been evaluated following receipt of a third dose of MMR vaccine.MethodsYoung adults aged 18–31 years with documented two doses of MMR vaccine received a third dose of MMR vaccine between July 2009 and October 2010. Rubella neutralizing antibody titers were assessed before, 1 month, and 1 year after receipt of a third dose of MMR vaccine.ResultsAmong 679 participants, 1.8% had rubella antibody titers less than 10 U/ml, immediately before vaccination, approximately 15 years after receipt of a second dose of MMR vaccine. One month after receipt of a third dose of MMR vaccine, average titers were 4.5 times higher and >50% of participants had a 4-fold boost. Response was highest among those with titers less than 10 U/ml prior to vaccination (geometric mean titer ratio = 18.8; 92% seroconversion) and decreased with increasing pre-vaccination titers. Average titers declined 1 year postvaccination but remained significantly higher than pre-vaccination levels. The proportion classified as low-positive antibody levels increased from 3% 1 month postvaccination to 24% 1 year postvaccination.ConclusionsVaccination with a third dose of MMR vaccine resulted in a robust boosting of rubella neutralizing antibody response that remained elevated 1 year later. Young adults with low rubella titers are more likely to benefit from a third dose of MMR vaccine.     

Durability of humoral immune responses to rubella following MMR vaccination

BackgroundWhile administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults.MethodsIn this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot.ResultsRubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women.ConclusionsCollectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.     

Seroprevalence and durability of rubella virus antibodies in a highly immunized population

BackgroundAlthough the administration of the measles-mumps-rubella (MMR) vaccine has been widespread in the United States for decades, gaps in vaccine coverage still persist for various reasons. The maintenance of herd immunity against rubella virus (RV) is important to controlling the spread and resurgence of rubella and congenital rubella syndrome.MethodsIn this study, we sought to assess the seroprevalence of RV-specific antibodies in an adult population from a defined geographic area in Olmsted County, MN, and the surrounding municipalities, with relatively high vaccine coverage and no documented evidence of circulating RV in the past 24 years. Rubella-specific IgG antibodies were measured by ELISA in a large set of serum samples (n = 1393) obtained from the Mayo Clinic Biobank. This cohort was 80.2% female and ranged from 20 to 44 years of age.ResultsIn total, 97.8% of subjects were seropositive for rubella-specific IgG antibodies, with a median titer of 40.56 IU/mL, suggesting a high degree of immunization; however, 2.2% of subjects were found to be seronegative. Interestingly, 25.1% of subjects were seropositive but had titers lower than 25 IU/mL, indicating either a population of low responders or individuals that could potentially be at risk of waning immunity. No significant associations or differences were found between RV-specific titers and demographic variables such as age, sex, or body mass index (BMI).ConclusionsA high rate of seropositivity for rubella was found among this young adult cohort, but a significant percent of the cohort had lower titers that may indicate poor initial vaccine response and potential risk if their antibody titers decline.     

Associations between markers of cellular and humoral immunity to rubella virus following a third dose of measles-mumps-rubella vaccine

IntroductionRubella virus (RV) was eliminated in the United States in 2004, although a small portion of the population fails to develop long-term immunity against RV even after two doses of the measles-mumps-rubella (MMR) vaccine. We hypothesized that inherent biological differences in cytokine and chemokine signaling likely govern an individual’s response to a third dose of the vaccine.MethodsHealthy young women (n = 97) were selected as study participants if they had either low or high extremes of RV-specific antibody titer after two previous doses of MMR vaccine. We measured cytokine and chemokine secretion from RV-stimulated PBMCs before and 28 days after they received a third dose of MMR vaccine and assessed correlations with humoral immune response outcomes.ResultsHigh and low antibody vaccine responders exhibited a strong pro-inflammatory cellular response, with an underlying Th1-associated signature (IL-2, IFN-γ, MIP-1β, IP-10) and suppressed production of most Th2-associated cytokines (IL-4, IL-10, IL-13). IL-10 and IL-4 exhibited significant negative associations with neutralizing antibody titers and memory B cell ELISpot responses among low vaccine responders.ConclusionIL-4 and IL-10 signaling pathways may be potential targets for understanding and improving the immune response to rubella vaccination or for designing new vaccines that induce more durable immunity.     

Comparing the rubella seronegativity in pregnant women who received one dose of rubella vaccine at different ages in Taiwan

IntroductionVaccination is the best strategy to prevent rubella and congenital rubella. The aim of our study was to assess the immunity to rubella and determine rubella virus antibody titers in pregnant women who were offered a single dose of rubella vaccine at different ages of their lives.MethodsA total 15,067 rubella IgG antibody test results for Taiwanese pregnant women who received routine prenatal checkup at Fooyin University Hospital from 1999 to 2014 were analyzed in this study. The women were divided into five birth cohorts in order to compare their rubella seronegativities and antibody titers according to the different period of rubella vaccination policy in Taiwan.ResultsThe total rubella seronegativity rate was 11.2% (95% CI: 10.7–11.7%) and the mean rubella antibody titers was 51.0 IU/mL (SD = 54.7 IU/mL). The junior school cohort has the lowest rubella seronegativity of 7.6% (95% CI: 6.9–8.2%). The seronegativities were significantly high in the preschool cohort and in the 15-month-old cohort, 14.9% (95% CI: 13.2–16.6%) and 14.8% (95% CI: 11.5–18.1%), respectively. The OR values were 2.1 (95% CI: 1.8–2.5, p < 0.001) in the preschool cohort and 2.2 (95% CI: 1.6–2.8, p < 0.001) in the 15-month-old cohort, respectively, against the junior school cohort. Women in the 15-month-old cohort have lowest average rubella IgG titer, 25.4 IU/mL.ConclusionThe total rubella seronegativity rate was 11.2% in all native pregnant women. Women who received one dose rubella vaccine at preschool and 15-month-old have highest seronegativities. The 15-month-old cohort has the lowest average rubella IgG titer. We recommend a revised catch-up immunization policy to women who received one dose rubella vaccine at a younger age.     

Effect of the third dose of BNT162b2 COVID-19 mRNA vaccine on anti-SARS-CoV-2 antibody levels in healthcare workers

PurposeAdministration of three doses of Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine was completed in Japan in the spring of 2022. This study aimed to evaluate the antibody responses, and kinetics of three doses of vaccine in healthcare workers (HCWs).Patients and methodsWe conducted a longitudinal cohort study with HCWs, who had no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, from a single hospital. Immunoglobulin G (IgG) titers of anti-SARS-CoV-2 spike protein (SP) and nucleocapsid protein (NP) titers were measured using an automated chemiluminescent enzyme immunoassay system.ResultsA total of 636 HCWs participated in the study. The anti-SP IgG titers decreased slowly after the second dose of the BNT162b2 vaccine in all participants, and robust antibody response was observed after the third dose of the vaccine. The peak anti-SP IgG titer after the third dose was approximately 4.1-fold higher than that after the first and second doses, and the rate of decrease in the anti-SP IgG titer after the third dose was significantly more gradual, than that after the second dose. After the second dose of vaccine, the antibody response was weaker in older participants than in younger participants, and in males than in females respectively, whereas the response to the third dose of vaccine did not differ significantly by sex or age. Adverse events following immunization were generally mild to moderate.ConclusionThe third dose of the BNT162b2 vaccine induced a significant and sustained increase in anti-SP IgG titers, and was generally safe and well-tolerated.     

Measles,mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine

BackgroundAntibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence.MethodsChildren vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4–6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects.ResultsMost of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892 mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with ≥2-fold experienced a slower decline (≤7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12–15 months and >15 months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens.ConclusionsThe rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.     

HLA genotypes and rubella vaccine immune response: Additional evidence

Recent population-based studies have demonstrated the genetic heritability of rubella vaccine response and assessed that the HLA system may explain about 20% of the inter-individual variance in humoral immune response to this vaccine. Our earlier studies compared HLA allelic associations with rubella vaccine-specific antibodies between two smaller cohorts of healthy Rochester, MN, children (346 and 396 subjects) after two doses of rubella-containing vaccine. This study found that specific HLA alleles were consistently associated with rubella-specific antibody titers (B*27:05, DPA1*02:01, and DPB1*04:01 alleles). The current study examined HLA associations in an independent larger cohort of 1012 healthy San Diego, CA, subjects (age 19–40 years) after rubella vaccine in order to replicate our previous findings in the Rochester subjects. Two HLA associations of comparable magnitudes were consistently observed between B*27:05 (median NT₅₀ Rochester cohort 48.9, p = 0.067; San Diego cohort 54.8, p = 0.047) and DPB1*04:01 (median NT₅₀ Rochester cohort 61.6, p < 0.001; San Diego cohort 70.8, p = 0.084) alleles and rubella virus-neutralizing antibody titers. Additional HLA alleles resulted in consistent effects on IL-6 production in both cohorts, but did not meet criteria for statistical significance. Our data suggest these HLA alleles play a role in rubella vaccine-induced immunity and provide the basis for future studies that may explain the mechanism(s) by which these HLA polymorphisms affect immune responses to rubella vaccine.     

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults

We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/μL greater for cases than controls (p = 0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change −0.04 (±0.18) log₁₀ copies/mL; p = 0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination.     

Humoral immunogenicity to measles,rubella, and varicella-zoster vaccines in biliary atresia children

To investigate the humoral immune response to measles, rubella, and varicella-zoster virus (VZV) vaccines in biliary atresia (BA) children before liver transplantation, we conducted the cross-sectional designed study. Fifty BA children (age, 3.6 ± 0.2 years; 24 girls) who had not yet received liver transplantation, and another 150 healthy controls (age, 4.0 ± 0.1 years; 78 girls) were recruited into this study to evaluate their primary humoral immune response to measles, rubella, and VZV vaccines. All of these BA children (n = 50) and controls (n = 150) received one dose of measles, one dose of measles–mumps–rubella (MMR), and one dose of VZV vaccine before our assessment. Serum samples were collected at least 1 month after the vaccination and serum immunoglobulin G (IgG) antibody to measles, rubella, and VZV were then determined by qualitative enzyme-linked immune-sorbent assay. The prevalence of seropositive rate of measles IgG antibody (84% vs. 96.7%; P = 0.002), rubella (82.0% vs. 98.7%; P < 0.001), and VZV (74% vs. 95.3%; P < 0.001) were significantly different between BA children and the controls after regular measles, MMR, and VZV vaccination before 2 years of age. In those BA children with seronegative VZV antibody after vaccination, two had VZV infection after the liver transplantation. This study indicated that humoral immunity to rubella, measles and VZV vaccines are significantly lower in BA children than the normal population by standard vaccine schedule.     

The effect of measles-mumps-rubella (MMR) immunization on the immune responses of previously immunized primary school children

Current policies for measles control call for administration of a second dose of vaccine to immunize those who failed to respond to the initial dose and to boost the responses of those with low levels of antibody. However, there has been concern expressed publicly that reimmunization may have adverse immunologic consequences. To determine the effects of reimmunization on immune responses, primary school children (N=38, mean age=6.14+/-0.35 years) with documented previous measles-mumps-rubella vaccine (MMR) immunization during infancy 4-5 years earlier were studied before and 1 month after receiving MMR as a part of routine reimmunization in Beer-Sheva, Israel. A substantial number of children were seronegative to measles (24%), mumps (34%) and rubella (44%). On reimmunization all seroconverted to mumps and rubella and all but one (92%) seroconverted to measles. The geometric mean titer of measles virus neutralizing antibody increased from 171 to 724 and the greatest increases occurred in those with the lowest pre-immunization titers. Moderate increases in levels of total IgM, IgG and IgE were detected in those with increases in antibody to measles virus. After reimmunization leukocyte counts decreased significantly from (5.8 x 10(6))+/-2.3 to (3.4 x 10(6))+/-0.7 ml(-1) (P=0.0001). The percentages of both CD4(+) and CD8(+) T cells decreased while the CD4:CD8 ratio remained unchanged. The percentage of CD56(+) natural killer (NK) cells increased from 5.2+/-2.7 to 7.2+/-2.8 (P=0.01). Functional assays showed improved lymphoproliferation in response to stimulation with phytohemagglutinin and tetanus toxoid and stable NK lytic activity. Therefore, reimmunization was accompanied by decreased leukocyte counts, but leukocyte function was unchanged or improved.     

Rubella antibodies in vertically and horizontally HIV-infected young adults vaccinated early in life and response to a booster dose in those with seronegative results

BackgroundVery limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life.MethodsProspective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards.ResultsTime since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm³; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels.ConclusionAs vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose.     

High rate of rubella seronegativity in perinatally-infected HIV women of childbearing age: A case-control study

Rubella infection is a vaccine preventable disease. Maternal infection during pregnancy may lead to congenital infection and severe foetal malformations. Thanks to antiretroviral therapy, perinatally HIV-infected women have better prognosis and are now experiencing pregnancy. We evaluated the rate of rubella seronegativity in a cohort of HIV perinatally-infected women of childbearing age. A high rate of seronegativity was found in this group as compared to age-matched non-perinatally infected HIV-infected women (34.5% vs 6.90%, p < 0.01). MMR administration before rubella testing was identified in 75.8% of perinatally-infected women (22/29) with a mean of 2 doses (range: 1–3 doses). HIV perinatally-infected women of childbearing age should be screened repeatedly for rubella immunity.     

Correlations between measles, mumps, and rubella serum antibody levels in Olmsted County school children

We examined correlations between serum antibody levels to determine whether individuals with low levels of antibody to one component of the measles, mumps, and rubella (MMR) vaccine were also likely to have low antibody levels to the other MMR vaccine components. Our results indicate that children who had a low antibody level to one component of the MMR vaccine had a modest probability of having a low antibody level to either of the other MMR vaccine components. Overall, we found small, but statistically significant, correlations between antibody levels that were largely unaffected by race, sex, age at immunization, and time since immunization. While the correlations we observed were modest, approximately 25% of our population was seronegative for at least one component of the MMR vaccine. Therefore, our results support the current policy of continuing to administer the trivalent MMR vaccine even when only a single low antibody titer is observed.     

Australian rubella serosurvey 2012–2013: On track for elimination?

BackgroundThe World Health Organization has targeted rubella virus for elimination regionally. Australia was one of the first countries to implement a nationally funded rubella immunisation program, in 1971, and conducts regular national rubella serosurveillance studies. We aimed to estimate the seroprevalence of rubella-specific IgG antibody in the Australian population by age and sex in 2012–2013, to compare the results with three previous serosurveys conducted in 1996–1999, 2002 and 2007 and to estimate the effective reproduction numbers (R_n).MethodsThis study used 2729 serum and plasma specimens, randomly selected from a specimen bank collected in 2012–2013 across Australia. Age groups included in the sample ranged from 1 to 49 years. Sera were tested for rubella-specific IgG-antibody using the Enzygnost anti-rubella IgG enzyme immunoassay and classified as positive, negative or equivocal according to rubella-specific IgG concentrations of >7 IU/ml, <3 IU/ml and 3–7 IU/ml, respectively.ResultsThe overall proportions seropositive, seronegative and equivocal for rubella-specific IgG were 92.1% (95% CI, 91.0–93.2), 6.7% (95% CI, 5.7–7.7) and 1.2% (95% CI, 0.8–1.6), respectively. The proportion of males seropositive was significantly lower than females in the 30–34 (83.1% vs. 96.8%, p = 0.003), 35–39 (86.1% vs. 96.3%, p = 0.02) and 40–44 (86.1% vs. 95.7%, p = 0.03) year age groups. R_n for rubella in 2012–2013 was estimated to be 0.33 (95% CI 0.28–0.39).DiscussionThe 2012–2013 national serosurvey showed levels of rubella-specific IgG seropositivity in the Australian population are relatively high with no evidence of decrease compared to previous serosurveys conducted in 1996–1999, 2002 and 2007. The lower proportion of seropositive males aged 30–44 years likely reflects the initial immunisation program targeting females only. To our knowledge this study represents the longest period of serosurveillance following introduction of a nationally funded rubella immunisation program. The lack of evidence of decreasing rubella-specific IgG seropositivity is therefore reassuring for Australia and other countries with longstanding high vaccine coverage.     

Waning antibodies in measles and rubella vaccinees--a longitudinal study

The evolution of measles- and rubella-specific serum IgG was followed in a longitudinal study in 224 young adolescent vaccinees, with or without boost vaccination before or during the 6.8-year observation period. Antibody titres were monitored by enzyme immuno assay (Enzygnost, Dade-Behring). After revaccination (second dose) rubella seropositivity rate increased from 92.1 to 100%, whereas measles seroprevalence (about 90%) did not significantly change between the paired sera. Significantly higher IgG (> three-fold) in the second serum of 5.2% (measles) and 7.8% (rubella) of participants with low antibodies (measles: < 1500 mIU; rubella < 40 IU) in first serum, suggest a secondary immune response (SIR) during the study period, only partially explained by revaccination. Excluding individuals with SIR, minimal annual antibody decay rates of -2.9% (confidence interval, CI: -0.7 to -4.8%) for rubella and -1.6% (CI: -0.1 to -3%) for measles were determined in participants with single dose vaccination. Thus, two-dose vaccination was adequate to protect women from rubella infection at least during childbearing age. Similarly only few individuals may become seronegative for measles again after successful vaccination due to minimal waning of low antibody levels (< 1500 mIU). However, as a result of a more rapid decay of high-titre (> 1500 mIU) antibodies (-2.4%/year), many vaccinees may eventually become susceptible to vaccine-modified measles (VMM) and consequently complicate measles control strategies.     

Associations between race,sex and immune response variations to rubella vaccination in two independent cohorts

Introduction

Immune response variations after vaccination are influenced by host genetic factors and demographic variables, such as race, ethnicity and sex. The latter have not been systematically studied in regard to live rubella vaccine, but are of interest for developing next generation vaccines for diverse populations, for predicting immune responses after vaccination, and for better understanding the variables that impact immune response.

Methods

We assessed associations between demographic variables, including race, ethnicity and sex, and rubella-specific neutralizing antibody levels and secreted cytokines (IFNγ, IL-6) in two independent cohorts (1994 subjects), using linear and linear mixed models approaches, and genetically defined racial and ethnic categorizations.

Results

Our replicated findings in two independent, large, racially diverse cohorts indicate that individuals of African descent have significantly higher rubella-specific neutralizing antibody levels compared to individuals of European descent and/or Hispanic ethnicity (p < 0.001).

Conclusion

Our study provides consistent evidence for racial/ethnic differences in humoral immune response following rubella vaccination.     

Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.