Vaccinia Vaccine Research Articles

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we generated two DNA vaccine candidates by integrating MERS-CoV Spike (S) gene into a replicating Vaccinia Tian Tan (VTT) vector. Compared to homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates, but also proposes a heterologous sequential immunization strategy worthy of further development.

Exploration of the cross-immunity between SARS-CoV and SARS-CoV-2 in mice

Aim: This study aimed to develop a universal vaccine that can effectively address future outbreaks of coronavirus infections. Materials & methods: We developed recombinant DNA vaccines and vaccinia vector vaccines specific for SARS-CoV and SARS-CoV-2 and evaluated them in BALB/c mice. Both cellular and humoral immune responses were analyzed. Results: Compared with those immunized with the SARS-CoV or SARS-CoV-2 vaccine alone, the cross-immune group exhibited a 21.2-fold increase in cellular immune response, an over 80-fold increase in binding antibodies and a 136.7-fold increase in neutralizing antibodies. The combination of recombinant DNA and vaccinia vaccines induced a stronger immune response than DNA vaccine immunization alone. Conclusion: This study demonstrated that cross-immunization with different coronaviruses can induce a broad immune response.

The association between BCG scars and self-reported chronic diseases: A cross-sectional observational study within an RCT of Danish health care workers

IntroductionThe live-attenuated vaccines Bacillus Calmette-Guérin (BCG) and Vaccinia have been associated with beneficial non-specific effects. We assessed the prevalence of BCG and Vaccinia vaccine scars in a cohort of Danish health care workers and investigated the association between the presence of vaccine scars and self-reported chronic diseases. MethodsCross-sectional study utilizing baseline data collected during 2020–2021 at enrollment in a BCG trial aiming to assess the effect of BCG vaccination on absenteeism and infectious disease morbidity during the SARS-COV-2 pandemic. In Denmark, Vaccinia was discontinued in 1977, and BCG was phased out in the early 1980s. We used logistic regression analysis (adjusted for sex, birth year, and smoking status) to estimate the association between scar status and chronic diseases, providing adjusted Odds Ratios (aORs) with 95 % Confidence Intervals, for participants born before 1977, and born from 1965 to 1976. ResultsThe cohort consisted of 1218 participants (206 males; 1012 females) with a median age of 47 years (Q1–Q3: 36–56). Among participants born 1965–1976 (n = 403), who experienced the phase-outs, having BCG and/or Vaccinia scar(s) vs. having no vaccine scars yielded an aOR of 0.51 (0.29–0.90) of self-reported chronic disease; an effect primarily driven by BCG. In the same birth cohort, having vaccine scar(s) was most strongly associated with a lower prevalence of chronic respiratory and allergic diseases; the aORs being 0.39 (0.16–0.97) and 0.39 (0.16–0.91), respectively. ConclusionHaving a BCG scar was associated with a lower prevalence of self-reported chronic disease.

Generation of recombinant mAbs to vaccinia virus displaying high affinity and potent neutralization.

Members of the Orthopoxvirus genus can cause severe infections in humans. Global vaccination against smallpox, caused by the variola virus, resulted in the eradication of the disease in 1980. Shortly thereafter, vaccination was discontinued, and as a result, a large proportion of the current population is not protected against orthopoxviruses. The concerns that the variola virus or other engineered forms of poxviruses may re-emerge as bioweapons and the sporadic outbreaks of zoonotic members of the family, such as Mpox, which are becoming more frequent and prevalent, also emphasize the need for an effective treatment against orthopoxviruses. To date, the most effective way to prevent or control an orthopoxvirus outbreak is through vaccination. However, the traditional vaccinia-based vaccine may cause severe side effects. Vaccinia immune globulin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of vaccine adverse reactions and was also used occasionally for the treatment of severe orthopoxvirus infections. However, this treatment carries many disadvantages and is also in short supply. Thus, a recombinant alternative is highly needed. In this study, two non-human primates were immunized with live vaccinia virus, producing a robust and diverse antibody response. A phage-display library was constructed based on the animal's lymphatic organs, and a panel of neutralizing monoclonal antibodies (mAbs), recognizing diverse proteins of the vaccinia virus, was selected and characterized. These antibodies recognized both mature virion and enveloped virion forms of the virus and exhibited high affinity and potent in vitro neutralization capabilities. Furthermore, these monoclonal antibodies were able to neutralize Mpox 2018 and 2022 strains, suggesting a potential for cross-species protection. We suggest that a combination of these mAbs has the potential to serve as recombinant therapy both for vaccinia vaccine adverse reactions and for orthopoxvirus infections. IMPORTANCE In this manuscript, we report the isolation and characterization of several recombinant neutralizing monoclonal antibodies (mAbs) identified by screening a phage-display library constructed from lymphatic cells collected from immunized non-human primates. The antibodies target several different antigens of the vaccinia virus, covering both mature virion and extracellular enveloped virion forms of the virus. We document strong evidence indicating that they exhibit excellent affinity to their respective antigens and, most importantly, optimal in vitro neutralization of the virus, which exceeded that of vaccinia immune globulin. Furthermore, we present the ability of these novel isolated mAbs (as well as the sera collected from vaccinia-immunized animals) to neutralize two Mpox strains from the 2018 to 2022 outbreaks. We believe that these antibodies have the potential to be used for the treatment of vaccinia vaccine adverse reactions, for other orthopoxvirus infections, and in cases of unexpected bioterror scenarios.

Safety and Efficacy of Post-Eradication Smallpox Vaccine as an Mpox Vaccine: A Systematic Review with Meta-Analysis.

According to the World Health Organization, 83,339 laboratory-confirmed cases, including 72 deaths, of mpox (formerly known as monkeypox), have been reported from 110 locations globally as of 20 December 2022, making the disease a public health concern. Most of the cases (56,171, 67.4%) were reported from countries in North America. Limited data on vaccine effectiveness in the current mpox outbreak are available. However, the modified vaccinia virus (smallpox vaccine) has been predicted to prevent or reduce the severity of the mpox infection. The present study of systematic review and meta-analysis aimed to evaluate the modified vaccinia vaccine's safety and efficacy on mpox by using reported randomized clinical trials. Following guidelines from the Cochrane Collaboration and PRISMA, multiple databases including PubMed, PLOS ONE, Google Scholar, British Medical Journal, and the U. S. National Library of Medicine were searched. Out of 13,294 research articles initially identified, 187 were screened after removing duplicates. Following the inclusion and exclusion criteria, the meta-analysis included ten studies with 7430 patients. Three researchers independently assessed the risk of bias in the included study. The pooled results suggest that the vaccinia-exposed group had fewer side effects when compared to the vaccinia naïve group (odds ratio: 1.66; 95% CI: 1.07-2.57; p = 0.03). Overall, the modified vaccinia has proven safe and effective in both vaccinia naïve and previously exposed groups, with higher efficacy in the previously exposed groups.

Monkeypox infection elicits strong antibody and B cell response against A35R and H3L antigens

Monkeypox virus (MPXV) resides in two forms; mature and enveloped, and depending on it, distinct proteins are displayed on the viral surface. Here, we expressed two MPXV antigens from the mature, and one from the enveloped form, and tested their reactivity to sera of 11 MPXV recoverees while comparing to sera from recently and past vaccinated individuals. 8 out of 11 recoverees exhibited detectable neutralization levels against Vaccinia Lister. Sera from all recoverees bound strongly to A35R and H3L antigens. Moreover, the responses to A35R were significantly higher within the recoverees compared to both recently and past vaccinated donors. Lastly, A35R- and H3L-specific IgG+ B cells ranging from 0.03-0.46% and 0.11-0.36%, respectively, were detected in all recoverees (A35R), and in 9 out of 11 recoverees (H3L). Therefore, A35R and H3L represent MPXV immune targets and could be used in a heat-inactivated serological ELISA for the identification of recent MPXV infection.

The role of antigen availability during B cell induction and its effect on sustained memory and antibody production after infection and vaccination-lessons learned from the SARS-CoV-2 pandemic.

The importance of antibodies, particularly neutralizing antibodies, has been known for decades. When examining the immune responses against a pathogen after a vaccination or infection it is easier to measure the levels of antigen-specific antibodies than the T-cell response, but it does not give the whole picture. The levels of neutralizing antibodies are harder to determine but give a better indication of the quality of the antibody response. The induction of long-lived antibody-secreting plasma cells is crucial for a persistent humoral immune response, which has been shown for example after vaccination with the vaccinia vaccine, where antibody levels have been shown to persist for decades. With the SARS-CoV-2 pandemic ravaging the world for the past years and the monumental effort in designing and releasing novel vaccines against the virus, much effort has been put into analysing the quantity, quality, and persistence of antibody responses.

Disease History, Pathogenesis, Diagnostics, and Therapeutics for Human Monkeypox Disease: A Comprehensive Review.

The monkeypox disease is a zoonotic-infectious disease that transmits between animals and humans. It is caused by a double-stranded DNA virus belonging to the Orthopoxvirus genus that is closely related to the variola virus -the causative agent of smallpox. Although monkeypox infections were endemic to Western and Central Africa, the newly emerging monkeypox outbreak spread to more than 90 non-African countries. With the exception of the PCR-confirmed case of a return from Nigeria to the United Kingdom, the ongoing outbreak is largely unrelated to travel. In the most recent wave, cases are characteristically males in their thirties. Risk factors include close and particularly sexual contact with an infected person, and contact with fomites, infected animals or aerosolized-infectious material. Clinical diagnosis of monkeypox is confirmed with nucleic-acid amplification testing of samples originating from vesicles or genital lesions and using real-time or conventional PCR. Other methods, such as electron microscopy, immunohistochemistry, and virus culture are costly and time-consuming. In addition to timely diagnosis and contact tracing, restrictive measures to limit spread, such as isolation of infected patients, preventing contact with wild animals, and isolation of animals suspected to be viral reservoirs have shown promise. Although there are no specific treatments for monkeypox disease, the experience with smallpox suggests that the vaccinia vaccine, cidofovir, tecovirimat, and vaccinia immune globulin (IVG) may be beneficial for monkeypox treatment. In this review, we provide an update on the human-monkeypox disease with a special emphasis on its pathogenesis, prevention, diagnostics, and therapeutic measures.

An Update on the Pharmacological Aspects of Vaccines and Antivirals for the Management of Monkeypox

Monkeypox is a self-limiting zoonotic disease caused by the monkeypox virus belonging to the genus of orthopox viruses. Initially considered an ‘African disease’, this infection has crossed the boundaries to affect other continents and it has raised tremendous concerns among the general public as well as the medical fraternity all over the world, particularly because of the lack of specific vaccinations and drugs for the management of the illness. Epidemiological evaluation of the current infection has reported that it is mainly transmitted through sexual contact in bisexual men, mostly whites, and in those with pre-existing human immunodeficiency virus infection. The most common presentations were skin rash, anogenital lesions, or mucosal lesions along with systemic symptoms. It has been established that the vaccines and drugs approved for the management of smallpox could be used for the management of the current monkeypox outbreak. Vaccinia Immune Globulin (VIG) and vaccines like JYNNEOS and ACAM2000 and antiviral drugs like tecovirimat, cidofovir (CDV), and brincidofovir are being considered for those patients with serious diseases. It is imperative for physicians to understand the pharmacological aspects of these drugs for delivering better care to patients with monkeypox, which is eventually essential for the containment of this infection. This review covers updates on vaccines as well as drugs for the prevention and management of monkeypox.

Human Monkeypox: An Emerging Zoonosis.

Human monkeypox is caused by a zoonotic Orthopoxvirus that resembles smallpox. It is challenging to identify the illness from varicella and smallpox. The rapid spread of cases across countries has raised serious concerns among public health officials around the world, prompting accelerated investigations to identify the origins and causes of the rapid expansion of cases. When people come into contact with infected animals, they may unintentionally contract monkeypox. The monkeypox virus is transferred by direct exposure to lesions, respiratory droplets, body fluids, and contaminated objects like blood. Fever, rash, and lymph nodes frequentswelling are clinical signs of monkeypox, which can cause a multitude of health problems. The disease's worldwide significance is shown by the advent of outbreaks outside of Africa. To understand the constantly shifting epidemiology of this disease that is reemerging, monkeypox cases require improved monitoring and case identification. Before smallpox's eradication and the consequent absence of immunization attempts, vaccinia vaccination provided coincidental protection to the monkeypox virus; however, monkeypox gained therapeutic relevance. Additionally, given that rural Africa is where monkeypox cases are most common, it is possible that underreporting could result in an underestimate of the pathogen's potential impact. In recent months, cases of human monkeypox have alarmingly increased in nations where the illness is not prevalent. The current monkeypox outbreak, in light of the COVID-19 pandemic, represents a fresh threat. Clinicians need to be aware of this novel scenario, which differs from previous epidemics' scenarios. The transmission of monkeypox should be reduced by the development of efficient solutions by global health systems.

An attenuated vaccinia vaccine encoding the severe acute respiratory syndrome coronavirus-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human angiotensin-converting enzyme 2 transgenic mice from severe acute respiratory syndrome coronavirus-2 and its variants.

As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2 S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants.

Monkeypox and the safety of the blood supply.

Monkeypox and the safety of the blood supply.

Repositioning potentials of smallpox vaccines and antiviral agents in monkeypox outbreak: A rapid review on comparative benefits and risks.

Background and aimsThere is a sought for vaccines and antiviral agents as countermeasures for the recent monkeypox outbreak. Here, we aimed to review and discuss the repurposing potentials of smallpox vaccines and drugs in monkeypox outbreaks based on their comparative benefits and risks. Therefore, we conducted this rapid review and discussed the repurposing potentials of smallpox vaccines and drugs in monkeypox infection.MethodsHere, we searched Google Scholar and PubMed for relevant information and data. We found many articles that have suggested the use of smallpox vaccines and antiviral drugs in monkeypox outbreaks according to the study findings. We read the relevant articles to extract information.ResultsAccording to the available documents, we found two replication‐competent and one replication‐deficient vaccinia vaccines were effective against Orthopoxvirus. However, the healthcare authorities have authorized second‐generation live vaccina virus vaccines against Orthopoxvirus in many countries. Smallpox vaccine is almost 85% effective in preventing monkeypox infection as monkeypox virus, variola virus, and vaccinia virus are similar. The United States and Canada have approved a replication‐deficient third‐generation smallpox vaccine for the prevention of monkeypox infection. However, the widely used second‐generation smallpox vaccines contain a live virus and replicate it into the human cell. Therefore, there is a chance to cause virus‐induced complications among the vaccinated subjects. In those circumstances, the available Orthopoxvirus inhibitors might be a good choice for treating monkeypox infections as they showed similar efficacy in monkeypox infection in different animal model clinical trials. Also, the combined use of antiviral drugs and vaccinia immune globulin can enhance significant effectiveness in immunocompromised subjects.ConclusionRepurposing of these smallpox vaccines and antiviral agents might be weapons to fight monkeypox infection. Also, we recommend further investigations of smallpox vaccines and Orthopoxvirus inhibitors in a human model study to explore their exact role in human monkeypox infections.

Monkeypox: A clinical update for paediatricians.

The global spread of human monkeypox disease, a zoonotic infection related to smallpox and endemic to West and Central Africa, presents serious challenges for health systems. As of July 2022, 14 533 cases have been reported world‐wide, leading to designation as a Public Health Emergency of International Concern. Monkeypox disease is spread from animals to humans through infected lesions or fluids; human–human transmission occurs through fomites, droplets or direct contact. Illness is usually self‐limiting, but severe disease can occur in specific groups ‐ particularly children, and people who are immunocompromised or pregnant. Clinical presentation may include fever, lymphadenopathy and skin rash, but the rash may occur without other symptoms. Complications can include secondary bacterial infection of skin lesions, vision loss from corneal involvement, pneumonia, sepsis and encephalitis. Diagnosis of monkeypox requires consideration of epidemiological, clinical and laboratory findings, with sensitive history‐taking, to elicit close contacts, critical. Supportive management is usually sufficient, but treatment options (where required) include antivirals and vaccinia immune globulin. A paucity of safety data for relevant antivirals may limit their use. There are two types of monkeypox vaccines: a replication‐competent vaccinia vaccine, the use of which is logistically and clinically complex, and a replication‐deficient modified vaccinia Ankara virus vaccine. Preparedness of health systems for addressing the current outbreak is constrained by historic underfunding for research, and compounded by stigma and discrimination against cases and affected communities. Key challenges in halting transmission include improving vaccine equity and countering discrimination against men who have sex with men to aid diagnosis and treatment.

Monkeypox Virus review

In 1958, the first case human infected by Poxivirus was detected in Democratic Republic of the Congo. This virus can produce after an incubation period of 5 to 21 a large spectrum of symptoms which can be severe, and, in many cases, medical care is necessary. The research of Monkeypox requires special laboratory conditions. Different tests can help to identify this virus in human specimens, like PCR and ELISA. Vaccinia vaccines prepared from viral variants can offer protection against monkeypox.

Features of the pathogenesis, epidemiology, diagnostics, approaches to the treatment and prevention of small pox, the current state of the problem in Ukraine and the world

Introduction. Monkey pox is an anthropozoonous disease caused by orthopoxvirus, characterized by fever, general intoxication and skin rash, in some cases it can lead to fatal consequences; an infectious disease covered by international health regulations (IHR). The causative agent of the disease is classified as a biological agent - agent of a biological weapon. Most of the monkeypox cases associated with the 2022 outbreak are in the Western Hemisphere. Purpose: study of data on etiological, pathogenetic, epidemiological aspects, modern approaches to the diagnosis, treatment and prevention of monkeypox, the state of the problem in Ukraine and the world. Materials and methods: to perform the task, a review of publications was conducted in electronic databases of medical publications PubMed Medline of the US National Library of Medicine (NLM), Cochrane Database of Systematic Reviews, CDC (Centers for Disease Control and Prevention) website of the federal agency of the Ministry of Health USA. Results: The second generation ACAM2000 and third generation JYNNEOS™ monkeypox vaccines are currently available. Both vaccines are able to create immunity against monkeypox. Post-exposure vaccination can help prevent or reduce the severity of monkeypox. ACAM2000 is a single-dose vaccinia vaccine licensed by the FDA for the prevention of smallpox. Full immunity is achieved 4 weeks after vaccination. FDA expanded access to investigational protocol allows use of ACAM2000 for monkeypox immunization during an outbreak. The immunogenicity and protective efficacy of ACAM2000 is equivalent to that of the first generation Dryvax® smallpox vaccine. Smallpox vaccine virus is used as a live attenuated virus in the smallpox vaccine. Cases of encephalitis and Guillain-Barré syndrome following smallpox vaccination show that the incidence varies not only from place to place, but also from year to year in the same place. For the purposes of containment of the outbreak, prevention to reduce the risk of transmission from person to person, immediate detection of new cases and surveillance measures are necessary. Health care workers who provide care to patients with suspected or confirmed monkeypox who work with their specimens should use standard precautions to control infection. Specimens taken from animals or humans suspected of having monkeypox should be handled in equipped laboratories by trained personnel. According to WHO recommendations, samples taken from patients should be appropriately labeled, prepared for transportation using triple packaging. To prevent the further spread of monkeypox through the animal trade, captive animals potentially infected with smallpox must be isolated from other animals and quarantined for 30 days. Conclusions: 1.The monkeypox virus, which used to be endemic to certain regions of Africa, is now a global concern, with cases increasingly being reported in regions of the Western Hemisphere. 2. In connection with the fact that transmission from person to person most often occurs through airborne droplets or through direct contact with the mucous secretions of an infected person, social distancing and contact tracing are advisable. 3. In the last 6 months, cases of monkeypox have been confirmed among middle-aged people, which can be explained by the loss of cross-immunity from the smallpox vaccine. 4. The monkeypox virus multiplies in the cytoplasm and matures, creating primary viremia. Manifestations of a severe course of monkeypox are bronchopneumonia, respiratory distress syndrome, encephalitis, chorioretinal scars on the retina, etc. To minimize the risk of complications, it is advisable to provide timely treatment. 5. Medical organizations around the world are focused on understanding how cases of monkeypox are increasingly occurring in countries in the Western Hemisphere. 6. The study of etiotropic methods of treating monkey pox is promising.

Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.

To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell–based vaccine, an H5N1-based viral vectored vaccinia vaccine Wyeth/IL-15/5Flu, versus the current standard-of-care, seasonal inactivated influenza vaccine (IIV) and unvaccinated conditions. Wyeth/IL-15/5Flu vaccination was coincident with increased mutation incidence and frequency across the influenza genome; however, mutations were not enriched within T cell epitope regions, but high allele frequency mutations within conserved hemagglutinin stem regions and PB2 mammalian adaptive mutations arose. Depletion of CD4+ and CD8+ T cell subsets led to reduced frequency of mutants in vaccinated mice; therefore, vaccine-mediated T cell responses were important drivers of virus diversification. Our findings suggest that Wyeth/IL-15/5Flu does not generate T cell escape mutants but increases stochastic events for virus adaptation by stringent bottlenecks.

The Disease Ecology, Epidemiology, Clinical Manifestations, Management, Prevention, and Control of Increasing Human Infections with Animal Orthopoxviruses.

Zoonotic orthopoxvirus outbreaks have occurred repeatedly worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camelpox in the Middle East and India, buffalopox in India, vaccinia in South America, and novel emerging orthopoxvirus infections in the United States, Europe, Asia, and South America. Waning smallpox immunity may increase the potential for animal-to-human transmission followed by further community transmission person-to-person (as demonstrated by monkeypox and buffalopox outbreaks) and by contact with fomites (as demonstrated by camelpox, cowpox, and, possibly, Alaskapox). The objectives of this review are to describe the disease ecology, epidemiology, clinical manifestations, prevention, and control of human infections with animal orthopoxviruses and to discuss the association with diminished population herd immunity formerly induced by vaccinia vaccination against smallpox. Internet search engines were queried with key words, and case reports, case series, seroprevalence studies, and epidemiologic investigations were found for review.

Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster

Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster

Serological Immunity to Smallpox in New South Wales, Australia.

The re-emergence of smallpox is an increasing and legitimate concern due to advances in synthetic biology. Vaccination programs against smallpox using the vaccinia virus vaccine ceased with the eradication of smallpox and, unlike many other countries, Australia did not use mass vaccinations. However, vaccinated migrants contribute to population immunity. Testing for vaccinia antibodies is not routinely performed in Australia, and few opportunities exist to estimate the level of residual population immunity against smallpox. Serological data on population immunity in Australia could inform management plans against a smallpox outbreak. Vaccinia antibodies were measured in 2003 in regular plasmapheresis donors at the Australian Red Cross Blood Service from New South Wales (NSW). The data were analysed to estimate the proportion of Australians in NSW with detectable serological immunity to vaccinia. The primary object of this study was to measure neutralising antibody titres against vaccinia virus. Titre levels in donor samples were determined by plaque reduction assay. To estimate current levels of immunity to smallpox infection, the decline in geometric mean titres (GMT) over time was projected using two values for the antibody levels estimated on the basis of different times since vaccination. The results of this study suggest that there is minimal residual immunity to the vaccinia virus in the Australian population. Although humoral immunity is protective against orthopoxvirus infections, cell-mediated immunity and immunological memory likely also play roles, which are not quantified by antibody levels. These data provide an immunological snapshot of the NSW population, which could inform emergency preparedness planning and outbreak control, especially concerning the stockpiling of vaccinia vaccine.