Antibody response to three-dose anti-SARS-CoV-2 mRNA-vaccination in treated solid cancer patients.

Solid cancer patients are at higher risk of SARS-CoV-2 infection and severe complications. Moreover, vaccine-induced antibody response is impaired in patients on anticancer treatment. In this retrospective, observational, hypothesis-generating, cohort study, we assessed the antibody response to the third dose of mRNA vaccine in a convenience sample of patients on anticancer treatment, comparing it to that of the primary two-dose cycle. Among 99 patients included, 62.6% were ≥60 years old, 32.3% males, 67.7% with advanced disease. Exactly 40.4% were receiving biological therapy, 16.2% chemotherapy only and 7.1% both treatments. After the third dose, seroconversion rate seems to increase significantly, especially in non-responders to two doses. Heterologous vaccine-type regimen (two-dose mRNA-1273 and subsequent tozinameran or vice versa) results in higher antibody levels. This explorative study suggests that repeated doses of mRNA-vaccines could be associated with a better antibody response in this population. Furthermore, heterologous vaccine-type three-dose vaccination seems more effective in this population. Since this is a hypothesis-generating study, adequately statistically powered studies should validate these results.

People With Human Immunodeficiency Virus Receiving Suppressive Antiretroviral Therapy Show Typical Antibody Durability After Dual Coronavirus Disease 2019 Vaccination and Strong Third Dose Responses.

BACKGROUND: Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose. METHODS: We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls. RESULTS: Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses. CONCLUSION: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccines in people living with HIV: A longitudinal cohort study.

To clarify the characteristics in immunogenicity and safety of inactivated SARS-Cov-2 vaccines among HIV-infected individuals, a longitudinal cohort study was performed on HIV-infected and HIV-uninfected participants with no history of COVID-19 infection and COVID-19 vaccine inoculation. Participants information and adverse events were collected. Blood samples were collected on the same day before vaccination, 21 days after the first shot, 28 days after the second shot, 6 months after the second vaccination and 14 days after the third dose to test anti-receptor-binding domain IgG antibody, viral load, CD4+, CD8+ T cell count. Our result showed that although HIV-infected adults with low nadir CD4+ T cell count ≤ 350 cells/mm3 generate significantly lower immune response after three shots of vaccine compared with HIV-negative controls, 100% of all the HIV-infected and healthy controls were seroconverted after the third shot. Seroconversion ratio and antibody level of 190 days after two shots of vaccination for HIV-infected with nadir CD4+ T cell count ≤ 350 were significantly lower than that of healthy controls. No significant difference was found in viral load among blood samples collected at each time points. CD4 and CD4/CD8 ratio value were found increased greatly after each shot of inoculation in HIV-infected individuals with nadir CD4+ T cell count ≤ 350. Multiple logistic regression analysis showed that among HIV-infected individuals, PLWH with CD4+ T cell count ≤ 350 were less likely experience seroconversion 21 days after the first shot, and less likely maintained antibody immunity 6 months post 2nd dose. Adverse events after each inoculation were not serious and recovered within 1 week. In conclusion, inactivated COVID-19 vaccine was safe and effective in people living with HIV after three shots of vaccination. HIV-infected individuals with low nadir CD4+ T cell count ≤ 350 was associated with a nonoptimal antibody response. Further vaccination strategies could be developed for those with low CD4+ T cell counts.

Antibody response to the third dose of inactivated COVID-19 vaccine in people living with HIV (PLWH): A longitudinal cohort.

The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T1 ), 180 days after the second dose (T2 ) and 35 days after the third dose (T3 ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T1 , T2 , and T3 time periods were analyzed, and the effects of age, vaccine brand, and CD4+ T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4+ T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.

Persistence of Immune Response Elicited by Three Doses of mRNA Vaccine against SARS-CoV-2 in a Cohort of Patients with Solid Tumors: A One-Year Follow-Up.

The role and durability of the immunogenicity of the BNT162b2 mRNA vaccine against severe acute respiratory virus 2 (SARS-CoV-2), in cancer patients one year after receiving the third dose have to be elucidated. We have prospectively evaluated the long-term immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in 55 patients undergoing active treatment. Neutralizing antibody (NT Ab) titers against Omicron variants and total anti-trimeric S IgG levels were measured one year after the third dose. Heparinized whole-blood samples were used for the assessment of the SARS-CoV-2 interferon-γ release assay (IGRA). Thirty-seven patients (67.3%) showed positive total anti-trimeric S IgG one year after the third dose. Looking at the T-cell response against the spike protein, the frequency of responder patients did not decrease significantly between six and twelve months after the third dose. Finally, less than 20% of cancer patients showed an undetectable NT Ab titer against BA.1 and BA.5 variants of concern (VOCs). Underlying therapies seem to not affect the magnitude or frequency of the immune response. Our work underlines the persistence of humoral and cellular immune responses against BNT162b2 in a cohort of cancer patients one year after receiving the third dose, regardless of the type of underlying therapy.

Early Immunogenicity and Safety of the Third Dose of BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Among Adults Older Than 60 Years: Real-World Experience.

BACKGROUND: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. METHODS: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys. RESULTS: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. CONCLUSIONS: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.

Neutralizing Activities Against the Omicron Variant After a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination.

BACKGROUND: The use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants. METHODS: A total of 224 individuals who completed the 2-dose CoronaVac for 6 months were included. We studied reactogenicity and immunogenicity after a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the messenger ribonucleic acid (mRNA) vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-month boosting intervals. RESULTS: The solicited adverse events were mild to moderate and well tolerated. Total receptor binding domain (RBD) immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T-cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222, and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval group. CONCLUSIONS: All 4 booster vaccines significantly increased binding and neutralizing antibodies in individuals immunized with 2 doses of CoronaVac. The present evidence may benefit vaccine strategies to thwart variants of concern, including the omicron variant.

Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine.

A third Comirnaty vaccine dose increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain antibody levels (median, 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (me 22-fold), Delta, (median, 43-fold), and Omicron (median, 8-fold) variants, but had less impact on S-reactive T-cell immunity in nursing home residents.

A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients.

BACKGROUND & AIMS: Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine. METHODS: Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored. RESULTS: The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue). CONCLUSION: After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses. LAY SUMMARY: The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.

Third dose of SARS-CoV-2 vaccine: A systematic review of 30 published studies.

We analyzed published studies on the efficacy and safety of the third dose of the COVID-19 vaccine in various general population settings. We conducted systematic searches of PubMed and EMBASE for series published in the English language through November 15, 2021, using the search terms "third" or "booster" or "three" and "dose" and "COVID-19" or "SARS-CoV-2." All articles were selected according to the MOOSE guidelines. The seroconversion risk after third doses was descriptively expressed as a pooled rate ratio ([seroconversion rate after the third dose]/[seroconversion rate after the second dose]). The search returned 30 studies that included a total of 2 734 437 vaccinated subjects. In more than 2 700 000 Israeli patients extracted from the general population, the reduction in the risk of infection ranged from 88% to 92%. Conversion rates for IgG anti-spike ranged from 95% to 100%. In cancer or immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses. A third dose seems necessary to protect against all COVID-19 infection, severe disease, and death risk.

Antibody titers after a third dose of the SARS-CoV-2 BNT162b2 vaccine in immunocompromised adults in Greece: Is a fourth dose necessary?

Real-world data suggest that protection against COVID-19 declines a few months after vaccination, particularly in the elderly and immunocompromised individuals. Our study aimed to analyze the humoral response induced by a third supplemental dose of BNT162b2 vaccine in a mixed group of immunocompromised individuals by determining anti-spike (anti-S) IgG antibody titers at baseline (pre-third vaccine dose) and 4 weeks after the dose. Serum samples were obtained from a total group of 85 immunocompromised individuals (history of cancer: n = 20, lymphoma: n = 4, leukemia: n = 3, transplant recipients: n = 4, autoimmune disease: n = 42, inflammatory disease: n = 6, autoimmune diabetes type 1: n = 6) all of whom had previously received a two-dose schedule of the vaccine. The average number of days between second and third dose was 139.6145 (±41.39071). The overall IgG GMCs 4 weeks postvaccination were increased by more than 35 times (fold change = 35.30, p < 0.001). Fold changes were not significantly correlated with underlying condition, age, sex nor with days between second and third dose. Considering the predominance of omicron variants in the current period and the results of studies showing a decrease in the effectiveness of the third dose after 10 weeks we highly recommend a fourth dose to this vulnerable population group.

A cohort analysis of SARS-CoV-2 anti-spike protein receptor binding domain (RBD) IgG levels and neutralizing antibodies in fully vaccinated healthcare workers.

OBJECTIVES: The waning of humoral immunity after COVID-19 vaccine booster (third dose) has not yet been fully evaluated. This study updates data on anti-SARS-CoV-2 spike protein receptor binding domain (S-RBD) binding antibodies (bAb) and neutralizing antibodies (NAb) levels in individuals with homologous vaccination 3-4 months after receiving the booster dose. METHODS: Fifty-five healthcare workers (HCW) from Padova University-Hospital were asked to collect serum samples for determining antibodies (Ab) at 12 (t12) and 28 (t28) days, at 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation, and 3-4 months after receiving the 3rd homologous booster dose. HCW were monitored weekly for SARS-CoV-2 infection. Ab titers were measured by two chemiluminescent immunoassays, one targeting the S-RBD immunoglobulin G (IgG), and one surrogate viral neutralization test (sVNT), measuring NAb. RESULTS: Twenty of the HCW had natural COVID-19 infection (COVID+) at different times, before either the first or the second vaccination. Median S-RBD IgG and NAb levels and their interquartile ranges 3-4 months after the 3rd dose were 1,076 (529-3,409) kBAU/L and 15.8 (11.3-38.3) mg/L, respectively, for COVID-, and 1,373 (700-1,373) kBAU/L and 21 (12.8-53.9) mg/L, respectively, for COVID+. At multivariate regression analyses, with age and gender included as covariates, S-RBD IgG bAb and sVNT NAb levels were closely associated with the time interval between serological determination and the 3rd vaccine dose (log10 ßcoeff=-0.013, p=0.012 and log10 ßcoeff=-0.010, p=0.025) for COVID+, whereas no such association was found in COVID- individuals. CONCLUSIONS: The third booster dose increases anti-SARS-CoV-2 Ab levels, elevated levels persisting for up to 3-4 months. Waning of Ab levels appears to be less pronounced for COVID+ individuals.

Transition to endemic: acceptance of additional COVID-19 vaccine doses among Canadian adults in a national cross-sectional survey.

BACKGROUND: Additional doses of COVID-19 vaccine have been proposed as solutions to waning immunity and decreased effectiveness of primary doses against infection with new SARS-CoV-2 variants. However, the effectiveness of additional vaccine doses relies on widespread population acceptance. We aimed to assess the acceptance of additional COVID-19 vaccine doses (third and annual doses) among Canadian adults and determine associated factors. METHODS: We conducted a national, cross-sectional online survey among Canadian adults from October 14 to November 12, 2021. Weighted multinomial logistic regression analyses were used to identify sociodemographic and health-related factors associated with third and annual dose acceptance and indecision, compared to refusal. We also assessed influences on vaccine decision-making, and preferences for future vaccine delivery. RESULTS: Of 6010 respondents, 70% reported they would accept a third dose, while 15.2% were undecided. For annual doses, 64% reported acceptance, while 17.5% were undecided. Factors associated with third dose acceptance and indecision were similar to those associated with annual dose acceptance and indecision. Previous COVID-19 vaccine receipt, no history of COVID-19 disease, intention to receive an influenza vaccine, and increasing age were strongly associated with both acceptance and indecision. Chronic illness was associated with higher odds of acceptance, while self-reported disability was associated with higher odds of being undecided. Higher education attainment and higher income were associated with higher odds of accepting additional doses. Minority first language was associated with being undecided about additional doses, while visible minority identity was associated with being undecided about a third dose and refusing an annual dose. All respondents reported government recommendations were an important influence on their decision-making and identified pharmacy-based delivery and drop-in appointments as desirable. Co-administration of COVID-19 and influenza vaccines was viewed positively by 75.5% of the dose 3 acceptance group, 12.3% of the undecided group, and 8.4% of the refusal group. CONCLUSIONS: To increase acceptance, targeted interventions among visible minority and minority language populations, and those with a disability, are required. Offering vaccination at pharmacies and through drop-in appointments are important to facilitate uptake, while offering COVID-19/influenza vaccine co-administration may have little benefit among those undecided about additional doses.

A SARS-CoV-2 Outbreak Among Nursing Home Residents Vaccinated with a Booster Dose of mRNA COVID-19 Vaccine.

This study describes a SARS-CoV-2 outbreak caused by the Delta (B.1.617.2) variant in a nursing home in Central Italy during October-November 2021. Trained interviewers collected data from residents, staff, and administration officers with an agreed informed consent procedure. Thirty-two (44.5%) out of 72 residents (median age 89 years) and six (26.1%) of 23 healthcare workers were found to be infected with SARS-CoV-2. Infections occurred more often among residents with a higher index of independence in daily living activities, suggesting an increased risk for those with more interactions. Twenty-five infected residents (78.1%) received the booster dose of mRNA anti-COVID-19 vaccine > 7 days before SARS-CoV-2 onset. Half of the infected residents had mild symptoms, and only three required hospitalisation, one of whom died from COVID-19 complications. The study underlines the effectiveness of a booster dose in providing a high protection against severe disease and hospitalisation even among vulnerable individuals infected with the Delta variant of concern.

Adverse Events Among Young Adults Following a Third Dose of Measles-Mumps-Rubella Vaccine.

BACKGROUND: A third measles-mumps-rubella vaccine (MMR) dose (MMR3) is recommended in the United States for persons at increased risk for mumps during outbreaks. MMR3 is also likely given to persons who might have received 2 doses of MMR but lack documentation. Since MMR3 safety data are limited, we describe adverse events in persons receiving MMR3 in a nonoutbreak setting. METHODS: Young adults with 2 documented MMR doses were administered MMR3. From 2 weeks before until 4 weeks after MMR3 receipt, participants reported daily on 11 solicited, common symptoms potentially associated with MMR. Weekly rate differences in post- vs prevaccination (baseline) were evaluated by Poisson regression. Baseline rates were subtracted from postvaccination rates of significantly different symptoms to estimate the number and percentage of participants with excess risk for symptoms post-MMR3. Descriptive analyses were performed for 3 postvaccination injection-site symptoms. RESULTS: The 662 participants were aged 18-28 years (median = 20 years); 56% were women. Headache, joint problems, diarrhea, and lymphadenopathy rates were significantly higher postvaccination vs baseline. We estimate that 119 participants (18%) reported more symptoms after MMR3 than prevaccination. By symptom, 13%, 10%, 8%, and 6% experienced increased symptoms of headache, joint problems, diarrhea, and lymphadenopathy, respectively, after MMR3. The median onset was Days 3-6 postvaccination; the median duration was 1-2 days. One healthcare visit for a potential vaccination-related symptom (urticaria) was reported. Injection-site symptoms were reported by 163 participants (25%); the median duration was 1-2 days. CONCLUSIONS: Reported systemic and local events were mild and transient. MMR3 is safe and tolerable among young adults.

One-year results of half-dose versus one-third-dose photodynamic therapy in chronic or recurrent central serous chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSC) is characterized by an accumulation of subretinal fluid (SRF) in the macula. It is usually treated by laser photocoagulation or photodynamic therapy (PDT) with consisting of different doses and power. This study aimed to compare the efficacy of half-dose PDT and one-third-dose PDT in chronic or recurrent CSC. METHODS: A retrospective review of patients with chronic or recurrent CSC who were treated with either a half-dose or one-third-dose PDT, and had follow up 12 months afterwards. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and resolution of subretinal fluid (SRF) at baseline as well as 1, 3, 6 and 12 months post-PDT were assessed. RESULTS: Forty-six eyes and 20 eyes received half-dose and one-third-dose PDT, respectively. The study showed efficacy of the one-third-dose PDT compared with half-dose PDT in BCVA improvement (0.10±0.04 logMAR for one-third-dose versus 0.17±0.04, for half-dose, P=0.148) and CRT improvement (125.6±24.6 µm for one-third-dose versus 139.1±16.54, for half-dose, P=0.933) at 12 months. The SRF recurrence rate was significantly higher in the one-third-dose PDT group compared with the half-dose PDT group (40.0% versus 15.2%, P=0.027) at 12-months. CONCLUSION: At 12 months, the one-third-dose PDT was effective in terms of BCVA and CRT improvement, when compared with half-dose PDT. However, this study showed that one-third-dose PDT had a higher recurrence rate of SRF.

Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults.

BACKGROUND: Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year. METHODS: Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt. RESULTS: Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level, <8 mIU/mL), and 23 (3.5%) had low antibody levels (8-120 mIU/mL). One month after MMR3 receipt, 1 subject (0.2%) was seronegative, and 6 (0.9%) had low neutralizing antibodies, with only 21 of 662 (3.2%) showing a ≥ 4-fold rise in neutralizing antibodies. One year after MMR3 receipt, no subject was seronegative, and 10 of 617 (1.6%) had low neutralizing antibody levels. CMI analyses showed low levels of spot-forming cells after stimulation, suggesting the presence of T-cell memory, but the response was minimal after MMR3 receipt. MeV IgG avidity did not correlate with findings of neutralization analyses. CONCLUSIONS: Most subjects were seropositive before MMR3 receipt, and very few had a secondary immune response after MMR3 receipt. Similarly, CMI and avidity analyses showed minimal qualitative improvements in immune response after MMR3 receipt. We did not find compelling data to support a routine third dose of MMR vaccine.

Waning immunity against mumps in vaccinated young adults, France 2013.

In 2013, 15 clusters of mumps were notified in France; 72% (82/114) of the cases had been vaccinated twice with measles-mumps-rubella vaccine. To determine whether the risk of mumps increased with time since the last vaccination, we conducted a case-control study among clusters in universities and military barracks. A confirmed case had an inflammation of a salivary gland plus laboratory confirmation in 2013. A probable case presented with inflammation of a salivary gland in 2013 either lasting for > 2 days or with epidemiological link to a confirmed case. Controls had no mumps symptoms and attended the same university course, student party or military barracks. We collected clinical and vaccination data via web questionnaire and medical records. We calculated adjusted odds ratios (aOR) using logistic regression. 59% (50/85) of cases and 62% (199/321) of controls had been vaccinated twice. The odds of mumps increased for twice-vaccinated individuals by 10% for every year that had passed since the second dose (aOR 1.10; 95% confidence interval (CI): 1.02-1.19; p = 0.02). Mumps immunity waned with increasing time since vaccination. Our findings contributed to the French High Council of Public Health's decision to recommend a third MMR dose during outbreaks for individuals whose second dose dates > 10 years.