Showing papers on "Vaccination published in 2020"

COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses.

Abstract: An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18–55 years of age. Two doses of 1–50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential.

Vaccine hesitancy: the next challenge in the fight against COVID-19.

Abstract: Vaccine hesitancy remains a barrier to full population inoculation against highly infectious diseases. Coincident with the rapid developments of COVID-19 vaccines globally, concerns about the safety of such a vaccine could contribute to vaccine hesitancy. We analyzed 1941 anonymous questionnaires completed by healthcare workers and members of the general Israeli population, regarding acceptance of a potential COVID-19 vaccine. Our results indicate that healthcare staff involved in the care of COVID-19 positive patients, and individuals considering themselves at risk of disease, were more likely to self-report acquiescence to COVID-19 vaccination if and when available. In contrast, parents, nurses, and medical workers not caring for SARS-CoV-2 positive patients expressed higher levels of vaccine hesitancy. Interventional educational campaigns targeted towards populations at risk of vaccine hesitancy are therefore urgently needed to combat misinformation and avoid low inoculation rates.

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.

Abstract: Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults.

Abstract: In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.

DNA vaccine protection against SARS-CoV-2 in rhesus macaques.

Abstract: The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

Attitudes Toward a Potential SARS-CoV-2 Vaccine: A Survey of U.S. Adults.

Abstract: Background Coronavirus disease 2019 (COVID-19) has rapidly instigated a global pandemic. Vaccine development is proceeding at an unprecedented pace. Once available, it will be important to maximize vaccine uptake and coverage. Objective To assess intent to be vaccinated against COVID-19 among a representative sample of adults in the United States and identify predictors of and reasons for vaccine hesitancy. Design Cross-sectional survey, fielded from 16 through 20 April 2020. Setting Representative sample of adults residing in the United States. Participants Approximately 1000 adults drawn from the AmeriSpeak probability-based research panel, covering approximately 97% of the U.S. household population. Measurements Intent to be vaccinated against COVID-19 was measured with the question, "When a vaccine for the coronavirus becomes available, will you get vaccinated?" Response options were "yes," "no," and "not sure." Participants who responded "no" or "not sure" were asked to provide a reason. Results A total of 991 AmeriSpeak panel members responded. Overall, 57.6% of participants (n = 571) intended to be vaccinated, 31.6% (n = 313) were not sure, and 10.8% (n = 107) did not intend to be vaccinated. Factors independently associated with vaccine hesitancy (a response of "no" or "not sure") included younger age, Black race, lower educational attainment, and not having received the influenza vaccine in the prior year. Reasons for vaccine hesitancy included vaccine-specific concerns, a need for more information, antivaccine attitudes or beliefs, and a lack of trust. Limitations Participants' intent to be vaccinated was explored before a vaccine was available and when the pandemic was affecting a narrower swath of the United States. Questions about specific information or factors that might increase vaccination acceptance were not included. The survey response rate was 16.1%. Conclusion This national survey, conducted during the coronavirus pandemic, revealed that approximately 3 in 10 adults were not sure they would accept vaccination and 1 in 10 did not intend to be vaccinated against COVID-19. Targeted and multipronged efforts will be needed to increase acceptance of a COVID-19 vaccine when one becomes available. Primary funding source Agency for Healthcare Research and Quality.

ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime–boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans. The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 induces an immune response in rhesus macaques and leads to reduced SARS-CoV-2 viral loads in respiratory tissues and an absence of pneumonia, but not to a reduction in nasal virus shedding, compared with unvaccinated animals.

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.

Abstract: A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1-8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity.

Abstract: Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.

HPV Vaccination and the Risk of Invasive Cervical Cancer.

Abstract: Background The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the rela...

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.

Factors Associated With US Adults' Likelihood of Accepting COVID-19 Vaccination.

Abstract: Importance The development of a coronavirus disease 2019 (COVID-19) vaccine has progressed at unprecedented speed. Widespread public uptake of the vaccine is crucial to stem the pandemic. Objective To examine the factors associated with survey participants’ self-reported likelihood of selecting and receiving a hypothetical COVID-19 vaccine. Design, Setting, and Participants A survey study of a nonprobability convenience sample of 2000 recruited participants including a choice-based conjoint analysis was conducted to estimate respondents’ probability of choosing a vaccine and willingness to receive vaccination. Participants were asked to evaluate their willingness to receive each hypothetical vaccine individually. The survey presented respondents with 5 choice tasks. In each, participants evaluated 2 hypothetical COVID-19 vaccines and were asked whether they would choose vaccine A, vaccine B, or neither vaccine. Vaccine attributes included efficacy, protection duration, major adverse effects, minor adverse effects, US Food and Drug Administration (FDA) approval process, national origin of vaccine, and endorsement. Levels of each attribute for each vaccine were randomly assigned, and attribute order was randomized across participants. Survey data were collected on July 9, 2020. Main Outcomes and Measures Average marginal component effect sizes and marginal means were calculated to estimate the relationship between each vaccine attribute level and the probability of the respondent choosing a vaccine and self-reported willingness to receive vaccination. Results A total of 1971 US adults responded to the survey (median age, 43 [interquartile range, 30-58] years); 999 (51%) were women, 1432 (73%) White, 277 (14%) were Black, and 190 (10%) were Latinx. An increase in efficacy from 50% to 70% was associated with a higher probability of choosing a vaccine (coefficient, 0.07; 95% CI, 0.06-0.09), and an increase from 50% to 90% was associated with a higher probability of choosing a vaccine (coefficient, 0.16; 95% CI, 0.15-0.18). An increase in protection duration from 1 to 5 years was associated with a higher probability of choosing a vaccine (coefficient, 0.05 95% CI, 0.04-0.07). A decrease in the incidence of major adverse effects from 1 in 10 000 to 1 in 1 000 000 was associated with a higher probability of choosing a vaccine (coefficient, 0.07; 95% CI, 0.05-0.08). An FDA emergency use authorization was associated with a lower probability of choosing a vaccine (coefficient, −0.03; 95% CI, −0.04 to −0.01) compared with full FDA approval. A vaccine that originated from a non-US country was associated with a lower probability of choosing a vaccine (China: −0.13 [95% CI, −0.15 to −0.11]; UK: −0.04 [95% CI, −0.06 to −0.02]). Endorsements from the US Centers for Disease Control and Prevention (coefficient, 0.09; 95% CI, 0.07-0.11) and the World Health Organization (coefficient, 0.06; 95% CI, 0.04-0.08), compared with an endorsement from President Trump were associated with higher probabilities of choosing a vaccine. Analyses of participants’ willingness to receive each vaccine when assessed individually yielded similar results. An increase in efficacy from 50% to 90% was associated with a 10% higher marginal mean willingness to receive a vaccine (from 0.51 to 0.61). A reduction in the incidence of major side effects was associated with a 4% higher marginal mean willingness to receive a vaccine (from 0.54 to 0.58). A vaccine originating in China was associated with a 10% lower willingness to receive a vaccine vs one developed in the US (from 0.60 to 0.50) Endorsements from the Centers for Disease Control and Prevention and World Health Organization were associated with increases in willingness to receive a vaccine (7% and 6%, respectively) from a baseline endorsement by President Trump (from 0.52 to 0.59 and from 0.52 to 0.58, respectively). Conclusions and Relevance In this survey study of US adults, vaccine-related attributes and political characteristics were associated with self-reported preferences for choosing a hypothetical COVID-19 vaccine and self-reported willingness to receive vaccination. These results may help inform public health campaigns to address vaccine hesitancy when a COVID-19 vaccine becomes available.

Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study

Abstract: COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID- 19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.

Understanding COVID-19 vaccine demand and hesitancy: A nationwide online survey in China.

Abstract: Background This study attempts to understand coronavirus disease 2019 (COVID-19) vaccine demand and hesitancy by assessing the public’s vaccination intention and willingness-to-pay (WTP). Confidence in COVID-19 vaccines produced in China and preference for domestically-made or foreign-made vaccines was also investigated. Methods A nationwide cross-sectional, self-administered online survey was conducted on 1–19 May 2020. The health belief model (HBM) was used as a theoretical framework for understanding COVID-19 vaccination intent and WTP. Results A total of 3,541 complete responses were received. The majority reported a probably yes intent (54.6%), followed by a definite yes intent (28.7%). The perception that vaccination decreases the chances of getting COVID-19 under the perceived benefit construct (OR = 3.14, 95% CI 2.05–4.83) and not being concerned about the efficacy of new COVID-19 vaccines under the perceived barriers construct (OR = 1.65, 95% CI 1.31–2.09) were found to have the highest significant odds of a definite intention to take the COVID-19 vaccine. The median (interquartile range [IQR]) of WTP for COVID-19 vaccine was CNY¥200/US$28 (IQR CNY¥100–500/USD$14–72). The highest marginal WTP for the vaccine was influenced by socio-economic factors. The majority were confident (48.7%) and completely confident (46.1%) in domestically-made COVID-19 vaccine. 64.2% reported a preference for a domestically-made over foreign-made COVID-19 vaccine. Conclusions The findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intent and WTP. It is important to improve health promotion and reduce the barriers to COVID-19 vaccination.

Acceptance of a COVID-19 Vaccine in Southeast Asia: A Cross-Sectional Study in Indonesia

Abstract: Introduction: Several vaccine candidates are being clinically tested in response to the 2019 coronavirus disease (COVID-19) pandemic. This study was conducted to assess the acceptance of a 50 or 95% effective COVID-19 vaccine, when it becomes available in southeast Asia, among the general population in Indonesia. Methods: A cross-sectional online survey was conducted between March 25 and April 6, 2020. Participants were asked if they would accept a free vaccine which was 95 or 50% effective. Using a logistic regression model, we assessed the associations between sociodemographic characteristics, exposure to COVID-19 information, or perceived risk of infection with acceptance of a hypothetical COVID-19 vaccine. Results: Among 1,359 respondents, 93.3% of respondents (1,268/1,359) would like to be vaccinated for a 95% effective vaccine, but this acceptance decreased to 67.0% (911/1,359) for a vaccine with 50% effectiveness. For a 95% effective vaccine, being a healthcare worker and having a higher perceived risk of COVID-19 infection were associated with higher acceptance, adjusted odds ratio (aOR): 2.01; 95%CI: 1.01, 4.00 and aOR: 2.21; 95%CI: 1.07, 4.59, respectively; compared to civil servants, being retired was associated with less acceptance (aOR: 0.15; 95%CI: 0.04, 0.63). For a 50% effective vaccine, being a healthcare worker was also associated with greater acceptance, aOR: 1.57; 95%CI: 1.12, 2.20. Conclusion: Acceptance of a COVID-19 vaccine was highly influenced by the baseline effectiveness of the vaccine. Preparing the general population to accept a vaccine with relatively low effectiveness may be difficult.

Determinants of COVID-19 Vaccine Acceptance in Saudi Arabia: A Web-Based National Survey.

Abstract: Background: Vaccine hesitancy is a potential threat to global public health. Since there is an unprecedented global effort to develop a vaccine against the COVID-19 pandemic, much less is known about its acceptance in the community. Understanding key determinants that influence the preferences and demands of a future vaccine by the community may help to develop strategies for improving the global vaccination program. The aim of this study was to assess the prevalence of the acceptance of COVID-19 vaccine and their determinants among people in Saudi Arabia. Methods: A web-based, cross-sectional study was conducted using snowball sampling strategy under a highly restricted environment. A bilingual, self-administered anonymous questionnaire was designed and sent to the study participants through social media plat-forms and email. Study participants were recruited across the country, including the four major cities (Riyadh, Dammam, Jeddah, and Abha) in Saudi Arabia. Key determinants that predict vaccine acceptance among respondents were modelled using logistic regression analysis. Of the 1000 survey invitees, 992 responded to the survey. Results: Of the 992 respondents, 642 showed interest to accept the COVID-19 vaccine if it is available. Willingness to accept the future COVID-19 vaccine is relatively high among older age groups, being married participants with education level postgraduate degree or higher (68.8%), non-Saudi (69.1%), employed in government sector (68.9%). In multivariate model, respondents who were above 45 years (aOR: 2.15; 95% CI: 1.08-3.21) and married (aOR: 1.79; 95% CI: 1.28-2.50) were significantly associated with vaccine acceptance (p < 0.05). Conclusion: Addressing sociodemographic determinants relating to the COVID-19 vaccination may help to increase uptake of the global vaccination program to tackle future pandemics. Targeted health education interventions are needed to increase the uptake of the future COVID-19 vaccine.

2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases

Abstract: To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.

COVID-19 herd immunity: where are we?

Abstract: Herd immunity is a key concept for epidemic control. It states that only a proportion of a population needs to be immune (through overcoming natural infection or through vaccination) to an infectious agent for it to stop generating large outbreaks. A key question in the current COVID-19 pandemic is how and when herd immunity can be achieved and at what cost. During the current COVID-19 pandemic, the concept of herd immunity has become a topic of much debate. This Comment examines the factors that determine it, discusses how far we have come and considers what it will take to reach herd immunity safely.

An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma.

Abstract: Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours1,2. We are testing melanoma FixVac (BNT111)—an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma—in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4+ and CD8+ T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination. Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4+ and CD8+ T-cell immunity.

BCG-induced trained immunity: can it offer protection against COVID-19?

Abstract: Bacillus Calmette–Guerin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19. Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.