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The tetravalent dengue vaccine (CYD-TDV) has been shown to provide protection against dengue disease over 5-year follow-up in participants with previous dengue infection, but increased the risk of dengue hospitalisation and severe dengue during long-term follow-up in those without previous dengue infection. WHO recommended pre-vaccination screening to identify those with previous dengue infection (ie, dengue seropositive) who would benefit from vaccination. We re-evaluated CYD-TDV efficacy in those identified as dengue seropositive using five commercially available immunoassays, and assessed immunoassay performance. We included participants in the immunogenicity subsets of the phase 3 CYD14 (NCT01373281) and CYD15 (NCT01374516) CYD-TDV efficacy trials, which enrolled children aged 2–16 years in 2011–12 in five countries in the Asia-Pacific region (CYD14) and five Latin American countries (CYD15). Participants assessed had received at least one injection of study drug (CYD-TDV or placebo) and had baseline samples available. We tested baseline samples by IgG-based immunoassays to classify baseline dengue serostatus, using two ELISAs (EUROIMMUN and Panbio) and three rapid diagnostic tests (RDTs; TELL ME FAST, SD BIOLINE, and OnSite). Vaccine efficacy in preventing symptomatic, hospitalised, and severe virologically confirmed dengue was determined for participants who tested positive by each immunoassay. The specificity and sensitivity of each immunoassay was determined as percentage negative and positive agreement compared with the reference algorithm, which used dengue plaque reduction neutralisation test with 50% and 90% cutoffs and non-structural protein 1 IgG ELISA results to assign baseline serostatus. Samples were available for 3967 participants, 2735 (69·0%) of whom were classified as seropositive by the reference algorithm. Vaccine efficacy against symptomatic virologically confirmed dengue in immunoassay-positive participants was high across all five immunoassays (EUROIMMUN ELISA 88·2% [95% CI 77·3 to 93·9], Panbio ELISA 87·6% [76·7 to 93·4], TELL ME FAST RDT 88·8% [67·0 to 96·2], SD BIOLINE RDT 82·8% [66·9 to 91·1], and OnSite RDT 89·7% [64·6 to 97·0]), as was vaccine efficacy against hospitalised virologically confirmed dengue (EUROIMMUN-ELISA 72·8% [38·9 to 87·9], Panbio ELISA 77·5% [52·8 to 89·3], TELL ME FAST RDT 92·4% [37·8 to 99·1], SD BIOLINE RDT 87·2% [54·5 to 96·4], and OnSite RDT 73·7% [–5·1 to 93·4]) and severe virologically confirmed dengue (EUROIMMUN ELISA 86·9% [–16·8 to 98·5], Panbio ELISA 91·3% [27·6 to 99·0], TELL ME FAST RDT 100·0% [not estimable to 100·0%], SD BIOLINE RDT 89·4% [9·6 to 98·8], and OnSite RDT 73·4% [–193·7 to 97·6]). The immunoassays exhibited high specificity (≥98·8% for all immunoassays apart from SD BIOLINE RDT) but variable sensitivities, with higher sensitivities observed for the ELISAs (EUROIMMUN 89·2% [87·9 to 90·3] and Panbio 92·5 [91·4 to 93·5]) than the RDTs (TELL ME FAST 52·5% [50·6 to 54·4], SD BIOLINE 71·1% [69·3 to 72·8], and OnSite 47·6% [45·7 to 49·5]). Our findings suggest that these immunoassays could be used for pre-vaccination screening for CYD-TDV as tools to assist risk stratification until more sensitive and convenient tests become available. Sanofi Pasteur.

Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies. We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis, randomly selected from all patients who started treatment with interferon beta between 1996 and 1999. Patients left the study if they changed or discontinued therapy. Antibodies were measured blindly, using antiviral neutralisation bioassays with high, medium, and low sensitivity, and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result. Patients developed neutralising antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods (0·64–0·70) than they were during antibody-negative periods (0·43–0·46; p>0·03). When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1·51 to 1·58 (p>0·03). Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months (log rank test 6·83, p=0·009). During this short-term study, presence of neutralising antibodies did not affect disease progression measured with the expanded disability status scale. Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug. In patients who are not doing well on interferon beta, the presence of such antibodies should prompt consideration about change of treatment.

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants. Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al . show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.

Sir Per Soelberg Sorensen and colleagues' study (Oct 11, p 1184)1 of the effects of neutralising antibodies against interferon beta on the clinical efficacy of interferon beta in patients with multiple sclerosis is flawed by a methodological tautology. Sorensen and colleagues use the effect of neutralising antibodies on relapse rate to define a clinically relevant titre, and then use the same cohort of patients to claim that neutralising antibodies affect the clinical efficacy of interferon beta. [...]it would be interesting to know whether the persistence of neutralising antibodies depended on the neutra-lising antibody titre, as found in earlier smaller series.5 In our opinion, a change of treatment should be considered in clinically active patients who are neutralising antibody negative, because clinical activity in such patients is not caused by a neutralising-antibody-mediated reduction of interferon beta efficacy, but probably by a genuine non-responsiveness to this treatment.

Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8%) animals presented titers 30.5IU/ml, through mouse neutralization test. After 180 days, 9 (64.3%) sera showed titers 30.5IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51IU/ml, and after 360 days, all animals showed titers < 0.5IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5IU/ml; at 270 days, 15 (71.4%), with titers 30.5IU/ml and at 360 days, 4 (19.0%), with titers 30.5IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers 30.5IU/ml. A resposta humoral com vacina anti-rábica inativada foi estudada em 35 bovinos mestiços de raça nelore, na região oeste do estado de São Paulo. Noventa dias após a primo-vacinação, 13 (92,8%) animais apresentaram títulos 30,5UI/ml, através da prova de soroneutralização em camundongos. Após 180 dias, 9 (64,3%) soros evidenciaram títulos 30,5UI/ml; após 270 dias, apenas 1 (7,1%) soro demonstrou título = 0,51 UI/ml. O grupo que recebeu dose de reforço 30 dias após primo-vacinação apresentou, dois meses depois, 21 animais com títulos > 0,5UI/ml. Aos 180 dias, 17 (80,9%) soros apresentaram títulos > 0,5UI/ml; aos 270 dias, 15 (71,4%) soros com títulos 30,5UI/ml; aos 360 dias, 4 (19,0%) com títulos 30,5UI/ml. O reforço proporcionou nível elevado de anticorpos, por um período de três meses ou mais e, 240 dias após a revacinação, 71,4% dos animais apresentou títulos 30,5UI/ml.

ln order to study the measles antibody behavior of three vaccination schedules, 684 children were divided into 4 Groups: Group A (341 vaccinated children under the age of one); Group B (101 children at the age of one); Group C (74 children under the age of one and one at the age of one); Group D (163 unvaccinated children with a history of measles in the past - Group control). Children of Group A presented lower rates and 25.9% of the age group under two did not show any measles antibodies. In Group B, all the children presented antibodies. In Group C onby 4.0% did not. In all age groups, the geometric mean HI antibody titers of Group A were lower than the valuesfound in the other groups. The age at vaccination was the factor of greater influence on the results of this study. Com o objetivo de estudar o comportamento dos anticorpos contra o sarampo após a vacinação, 684 crianças foram divididas em 4 grupos: Grupo A (341 crianças vacinadas abaixo de um ano de idade); Grupo B (101 crianças com um ano de idade); Grupo C (79 crianças com 2 doses, uma abaixo de um ano e outra com um ano de idade); Grupo D (163 crianças não vacinadas com história prévia de sarampo - grupo controle). Verificou-se que as crianças do Grupo A apresentavam baixas taxas de anticorpos protetores, sendo que em 25,9 % delas, na faixa etária de menores de dois anos, tais anticorpos não foram detectados, contra nenhum caso do Grupo C e 4,0% do Grupo B. As médias geométricas dos títulos de anticorpos HI do Grupo A foram inferiores às encontradas para os outros grupos. A idade da vacinação foi o fator de maior influência nos resultados deste estudo.

We conducted a severe acute respiratory syndrome coronavirus 2 antibody seroprevalence study among >2,000 domestic cats from 4 countries during the first coronavirus disease wave in Europe. We found 4.4% seroprevalence using a virus neutralization test and 4.3% using a receptor-binding domain ELISA, demonstrating probable human-to-cat transmission.

ObjectivesTo evaluate the restart of the German Bundesliga (football (soccer)) during the COVID-19 pandemic from a medical perspective.MethodsParticipants were male professional football players from the two highest German leagues and the officials working closely with them. Our report covers nine match days spread over 9 weeks (May to July 2020). Daily symptom monitoring, PCR testing for SARS-CoV-2 RNA twice weekly, and antibody tests (on two occasions—early during the phase in May 2020 and in the week of the last match) were conducted. Target variables were: (1) onset of typical COVID-19 symptoms, (2) positive PCR results, and (3) IgG seroconversion against SARS-CoV-2. All detected seroconversions were controlled by neutralisation tests.FindingsSuspicious symptoms were reported for one player; an immediate additional PCR test as well as all subsequent diagnostic and antibody tests proved negative for coronavirus. Of 1702 regularly tested individuals (1079 players, 623 officials members), 8 players and 4 officials tested positive during one of the first rounds of PCR testing prior to the onset of team training, 2 players during the third round. No further positive results occurred during the remainder of the season. 694 players and 291 officials provided two serum samples for antibody testing. Nine players converted from negative/borderline to positive (without symptoms); two players who initially tested positive tested negative at the end of the season. 22 players remained seropositive throughout the season. None of the seroconversions was confirmed in the neutralisation test.ConclusionProfessional football training and matches can be carried out safely during the COVID-19 pandemic. This requires strict hygiene measures including regular PCR testing.