Revisiting the potential role of BCG and MMR vaccines in COVID-19.

Despite the development and deployment of effective COVID-19 vaccines, many regions remain poorly covered. Seeking alternative tools for achieving immunity against COVID-19 remains to be of high importance. "Trained immunity" is the nonspecific immune response usually established through administering live attenuated vaccines and is a potential preventive tool against unrelated infections. Evidence regarding a possible protective role for certain live attenuated vaccines against COVID-19 has emerged mainly for those administered as part of childhood vaccination protocols. This review summarizes the relevant literature about the potential impact of Bacille Calmette-Guérin (BCG) and measles, mumps and rubella (MMR) vaccines on COVID-19. Existing available data suggest a potential role for BCG and MMR in reducing COVID-19 casualties and burden. However, more investigation and comparative studies are required for a better understanding of their impact on COVID-19 outcomes.

Varicella zoster virus reactivation following COVID-19 vaccination: a report of 3 cases.

BACKGROUND: The advent of vaccination against COVID-19 brought great expectations for the control of the pandemic. As novel vaccines, much of the associated side effects were unknown. Currently, an increasing number of reports from side effects of COVID-19 vaccines have been published, namely on cutaneous reactions. These are of utmost importance to increase our knowledge about possible undesirable effects and its prevention. METHODS: We describe a series of 3 cases who presented with varicella zoster virus (VZV) reactivation following the first dose of 3 different COVID-19 vaccines. RESULTS: Three patients sought their Family Doctor after developing typical lesions of VZV reactivation, following a period of 3-13 days after COVID-19 vaccination. None was under immunosuppressive therapy. The 3 patients recovered in a few weeks and the subsequent doses of the vaccines were administered, without recurrence of the symptoms. CONCLUSIONS: These cases highlight the possibility of VZV reactivation after the first dose of COVID-19 vaccines. Family Doctors should be aware of this event and play an important role informing and reassuring local communities for this possible vaccine reaction.

Sequential Delivery of Live Attenuated Influenza Vaccine and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Ferret Model Can Reduce SARS-CoV-2 Shedding and Does Not Result in Enhanced Lung Pathology.

Cocirculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in coinfected patients. The initial lack of a readily available coronavirus disease 2019 (COVID-19) vaccine has reinforced the importance of influenza vaccine programs during the COVID-19 pandemic. Live attenuated influenza vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration influences the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV was administered to ferrets 3 days before or after SARS-CoV-2 infection. LAIV administration did not exacerbate the SARS-CoV-2 disease course or lung pathology with either regimen. In addition, LAIV administered before SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract. This study demonstrated that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.

COVID-19 Infection Among Women in Iran Exposed vs Unexposed to Children Who Received Attenuated Poliovirus Used in Oral Polio Vaccine.

Importance: Live attenuated vaccines may provide short-term protection against infectious diseases through stimulation of the innate immune system. Objective: To evaluate whether passive exposure to live attenuated poliovirus is associated with diminished symptomatic infection with SARS-CoV-2. Design, Setting, and Participants: In a longitudinal cohort study involving 87 923 people conducted between March 20 and December 20, 2020, the incidence of COVID-19 was compared between 2 groups of aged-matched women with and without exposure to live attenuated poliovirus in the oral polio vaccine (OPV). Participants were people receiving health care services from the Petroleum Industry Health Organization and residing in 2 cities in Iran (ie, Ahwaz and Shiraz). Participants were women aged 18 to 48 years whose children were aged 18 months or younger and a group of age-matched women from the same residence who had had no potential exposure to OPV. Exposures: Indirect exposure to live attenuated poliovirus in OPV. Main Outcomes and Measures: Symptomatic COVID-19, diagnosed by reverse transcription-polymerase chain reaction. Results: After applying the inclusion and exclusion criteria, 419 mothers (mean [SD] age, 35.5 [4.9] years) indirectly exposed to the OPV and 3771 age-matched women (mean [SD] age, 35.7 [5.3] years) who had no exposure to OPV were available for analysis. COVID-19 was diagnosed in 1319 of the 87 923 individuals in the study population (151 per 10 000 population) during the study period. None of the mothers whose children received OPV developed COVID-19 after a median follow-up of 141 days (IQR, 92-188 days; range, 1-270 days); 28 women (0.74%; 95% CI, 0.47%-1.02%) in the unexposed group were diagnosed with COVID-19 during the 9 months of the study. Point-by-point comparison of the survival curves of the exposed and unexposed groups found that indirect exposure to OPV was significantly associated with decreased COVID-19 acquisition; probability of remaining without infection was 1.000 (95% CI, 1.000-1.000) in the exposed group vs 0.993 (95% CI, 0.990-0.995) in the unexposed group after 9 months (P < .001). Conclusions and Relevance: In this cohort study, indirect exposure to live attenuated poliovirus was associated with decreased symptomatic infection with COVID-19. Further study of the potential protective effect of OPV should be conducted, especially in nations where OPV is already in use for polio prevention and specific COVID-19 vaccines are delayed, less affordable, or fail to meet demand.

Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1.

The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

A Newcastle disease virus expressing a stabilized spike protein of SARS-CoV-2 induces protective immune responses.

Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine candidate based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here, we show that the NDV vector expressing an optimized spike antigen (NDV-HXP-S) is a versatile vaccine inducing protective antibody responses. NDV-HXP-S can be administered intramuscularly as inactivated vaccine or intranasally as live vaccine. We show that NDV-HXP-S GMP-produced in Vietnam, Thailand and Brazil is effective in the hamster model. Furthermore, we show that intramuscular vaccination with NDV-HXP-S reduces replication of tested variants of concerns in mice. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters.

Genetically Engineered Live-Attenuated Middle East Respiratory Syndrome Coronavirus Viruses Confer Full Protection against Lethal Infection.

There are no approved vaccines against the life-threatening Middle East respiratory syndrome coronavirus (MERS-CoV). Attenuated vaccines have proven their potential to induce strong and long-lasting immune responses. We have previously described that severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a virulence factor. Based on this knowledge, a collection of mutants carrying partial deletions spanning the C-terminal domain of the E protein (rMERS-CoV-E*) has been generated using a reverse genetics system. One of these mutants, MERS-CoV-E*Δ2in, was attenuated and provided full protection in a challenge with virulent MERS-CoV after a single immunization dose. The MERS-CoV-E*Δ2in mutant was stable as it maintained its attenuation after 16 passages in cell cultures and has been selected as a promising vaccine candidate.IMPORTANCE The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. Using a reverse genetics system developed in our laboratory, an infectious cDNA clone of MERS-CoV was engineered. Using this cDNA, we sequentially deleted several predicted and conserved motifs within the envelope (E) protein of MERS-CoV, previously associated with the presence of virulence factors. The in vitro and in vivo evaluation of these deletion mutants highlighted the relevance of predicted linear motifs in viral pathogenesis. Two of them, an Atg8 protein binding motif (Atg8-BM), and a forkhead-associated binding motif (FHA-BM), when deleted, rendered an attenuated virus that was evaluated as a vaccine candidate, leading to full protection against challenge with a lethal dose of MERS-CoV. This approach can be extended to the engineering of vaccines protecting against the new pandemic SARS-CoV-2.

Doctor-Should I get the COVID-19 vaccine? Infection and immunization in individuals with neuromuscular disorders.

The clinical course of neuromuscular disorders (NMDs) can be affected by infections, both in immunocompetent individuals, and in those with reduced immunocompetence due to immunosuppressive/immunomodulating therapies. Infections and immunizations may also trigger NMDs. There is a potential for reduced efficacy of immunizations in patients with reduced immunocompetence. The recent vaccination program for coronavirus disease-2019 (COVID-19) raises several questions regarding the safety and efficacy of this vaccine in individuals with NMDs. In this Practice Topic article, we address the role of vaccine-preventable infections in NMDs and the safety and efficacy of immunization in individuals with NMDs, with emphasis on vaccination against COVID-19.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 Influenza Season.

This report updates the 2019-20 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2019;68[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Most influenza vaccines available for the 2020-21 season will be quadrivalent, with the exception of MF59-adjuvanted IIV, which is expected to be available in both quadrivalent and trivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 23, 2019; February 26, 2020; and June 24, 2020. Primary updates to this report include the following two items. First, the composition of 2020-21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. Second, recent licensures of two new influenza vaccines, Fluzone High-Dose Quadrivalent and Fluad Quadrivalent, are discussed. Both new vaccines are licensed for persons aged ≥65 years. Additional changes include updated discussion of contraindications and precautions to influenza vaccination and the accompanying Table, updated discussion concerning use of LAIV4 in the setting of influenza antiviral medication use, and updated recommendations concerning vaccination of persons with egg allergy who receive either cell culture-based IIV4 (ccIIV4) or RIV4.The 2020-21 influenza season will coincide with the continued or recurrent circulation of SARS-CoV-2 (the novel coronavirus associated with coronavirus disease 2019 [COVID-19]). Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient illnesses, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html.This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2020-21 season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration (FDA)-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

New disease old vaccine: Is recombinant BCG vaccine an answer for COVID-19?

Mycobacterium bovis BCG, a live attenuated tuberculosis vaccine offers protection against disseminated TB in children. BCG exhibits heterologous protective effects against unrelated infections and reduces infant mortality due to non-mycobacterial infections. Recent reports have suggested that BCG vaccination might have protective effects against COVID-19, however it is highly unlikely that BCG vaccine in its current form can offer complete protection against SARS-CoV-2 infection due to the lack of specific immunity. Nonetheless, recombinant BCG strains expressing antigens of SARS-CoV-2 may offer protection against COVID-19 due to the activation of innate as well as specific adaptive immune response. Further proven safety records of BCG in humans, its adjuvant activity and low cost manufacturing makes it a frontrunner in the vaccine development to stop this pandemic. In this review we discuss about the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.

Potential of live pathogen vaccines for defeating the COVID-19 pandemic: History and mechanism.

The whole world has entered a terrible crisis with a huge and increasing number of human deaths and economic losses in fighting the pandemic of COVID-19 caused by the novel coronavirus termed SARS-CoV-2. The live pathogen vaccine (LPV) strategy, which originated in ancient China for fighting smallpox, has been applied successfully by US military recruits for decades to control acute respiratory diseases caused by types 4 and 7 adenoviruses. This strategy has also been widely employed in veterinary medicine. These facts suggest a fast way out of the current pandemic crisis, namely that SARS-CoV-2 could be directly used as a live vaccine. Beyond the two traditional mechanisms to guarantee the LPV's safety (the LPV seed strain is properly selected; the LPV is inoculated bypassing the respiratory sites of pathology), three novel mechanisms to further ensure the LPV's safety are available (the virus replication is inhibited with early use of an antiviral drug; symptomatic LPV recipients are cured with convalescent plasma; the LPV is inoculated in the hot season). This LPV strategy has multiple potential advantages over other options and could reduce morbidity and mortality greatly as well as the economic loss caused by the pandemic. The safety and efficacy of this strategy should be investigated strictly using animal experiments and clinical trials, and even if the experiments and trials all support the strategy, it should be implemented with enough caution.