Dose Of Inactivated Vaccine Research Articles

Protection of Spanish Ibex (Capra pyrenaica) against Bluetongue Virus Serotypes 1 and 8 in a Subclinical Experimental Infection

Many wild ruminants such as Spanish ibex (Capra pyrenaica) are susceptible to Bluetongue virus (BTV) infection, which causes disease mainly in domestic sheep and cattle. Outbreaks involving either BTV serotypes 1 (BTV-1) and 8 (BTV-8) are currently challenging Europe. Inclusion of wildlife vaccination among BTV control measures should be considered in certain species. In the present study, four out of fifteen seronegative Spanish ibexes were immunized with a single dose of inactivated vaccine against BTV-1, four against BTV-8 and seven ibexes were non vaccinated controls. Seven ibexes (four vaccinated and three controls) were inoculated with each BTV serotype. Antibody and IFN-gamma responses were evaluated until 28 days after inoculation (dpi). The vaccinated ibexes showed significant (P<0.05) neutralizing antibody levels after vaccination compared to non vaccinated ibexes. The non vaccinated ibexes remained seronegative until challenge and showed neutralizing antibodies from 7 dpi. BTV RNA was detected in the blood of non vaccinated ibexes from 2 to the end of the study (28 dpi) and in target tissue samples obtained at necropsy (8 and 28 dpi). BTV-1 was successfully isolated on cell culture from blood and target tissues of non vaccinated ibexes. Clinical signs were unapparent and no gross lesions were found at necropsy. Our results show for the first time that Spanish ibex is susceptible and asymptomatic to BTV infection and also that a single dose of vaccine prevents viraemia against BTV-1 and BTV-8 replication.

Statins and Influenza: Can We Move Forward?

Currently, the 2 main strategies for control of influenza are immunization and antiviral drugs. However, despite increasing uptake of influenza vaccine among the highest risk groups—namely, the elderly and persons with underlying cardiopulmonary diseases—morbidity and mortality from influenza continues to rise in the United States [ 1 ]. This paradox has stimulated a heated debate regarding the true efficacy of influenza vaccination in older persons [ 2 , 3 ]. Some investigators suggest efficacy may be negligible in this group, and even the most optimistic proponents of immunization concede that the current licensed standard dose of inactivated vaccine is less immunogenic and protective in older persons than in young healthy persons [ 4 , 5 , 6 ]. Antiviral therapy, principally with neuraminidase inhibitors, has been shown repeatedly in placebo-controlled trials to be effective when administered to both young and old outpatients early in the course of illness [ 7 , 8 ]. Although controlled studies in inpatients are strikingly absent, one observational analysis from Toronto noted a 79% reduction in mortality in patients treated with a neuraminidase inhibitor, even when administered after the 48-hour window following symptom onset [ 9 ]. Despite availability of vaccine and antivirals, additional therapeutic measures for influenza would be welcomed. In this issue of the Journal, Vandermeer and collaborators report that statin use is associated with reduced mortality during and after hospitalization with influenza infection [ 10 ]. The investigators analyzed 30-day mortality in 3043 patients hospitalized with influenza in 10 states as part of the Centers for Disease Control and Prevention’s Emerging Infections Program. After adjusting for other variables, such as age, underlying medical conditions, and influenza vaccination, they reported a striking 41% reduction in mortality (odds ratio, 0.59 [95% confidence interval, .38‐.92]) in persons on statins either prior to or during hospi

Report of the 7th meeting on Evaluation of Pandemic Influenza Vaccines in Clinical Trials, World Health Organization, Geneva, 17–18 February 2011

On February 17-18, 2011, the World Health Organization convened the 7th meeting on "The Evaluation of Pandemic Influenza Vaccines in Clinical Trials" to review the progress made on pandemic A (H1N1) 2009 vaccines and the evaluation of their effectiveness in the field, especially in children less than 3 years of age and in pregnant women. Other topics to be addressed included a comparison of egg- and cell culture-based influenza vaccines, technical issues related to vaccine strain development and vaccine potency, and the status of development of prototype influenza vaccines using new technologies. Pandemic A (H1N1) vaccines were safe in young children, pregnant women and immunocompromized individuals. Overall effectiveness of inactivated A (H1N1) vaccines for all ages was found to vary between 72% and 100% in different countries and with different vaccine preparations. Effectiveness of pandemic A (H1N1) 2009 live attenuated vaccine was estimated to be approximately 80% in pediatric populations in the USA. A single dose of inactivated vaccine adjuvanted with AS03, MF59 or AF03 induced protective immunity in young children and pregnant women. However, unadjuvanted vaccines as well as low dose adjuvanted vaccines (1.9 μg HA) required two doses to elicit protective antibody levels in these populations. Clinical trials of influenza vaccines developed using new technologies showed they were well tolerated and induced antibody and/or T cell immune responses to viral proteins. Further studies are warranted to validate novel immunological criteria for evaluation and licensing of such new influenza vaccine concepts. On the regulatory side, work should be undertaken to harmonize the results of serological tests used to evaluate the immunogenicity of traditional influenza vaccines.

Virus aggregating peptide enhances the cell-mediated response to influenza virus vaccine

Given the poor immunogenicity of current H5N1 influenza vaccines, additives and adjuvants remain a viable solution for increasing efficacy. Here, we demonstrate that a 20-amino acid peptide (EB) possessing influenza antiviral activity also enhances the immune response to H5N1 vaccination in mice. The addition of EB to formalin-inactivated whole-virus vaccine induced virion aggregation and these aggregates were readily engulfed by phagocytic cells in vitro. In vivo, mice vaccinated with a suboptimal dose of inactivated vaccine containing EB peptide had reduced morbidity, improved viral clearance, and faster recovery than mice receiving vaccine alone. This phenomenon was not accompanied by an increase in virus-specific antibodies. Instead, cell-mediated immunity was enhanced as demonstrated by increased interferon-γ production from splenocytes. This data demonstrates that the EB peptide may a useful adjuvant for boosting the efficacy of poorly immunogenic influenza vaccines.

Superior protection provided by a single dose of MF59-adjuvanted whole inactivated H5N1 influenza vaccine in type 1 diabetic mice

Vaccination is the preferred strategy for the prevention of influenza virus infection. Both H5N1 subunit and split vaccines have shown poor immunogenicity in clinical trials thus far. Therefore, it is urgent to develop more immunogenic and antigen-sparing H5N1 influenza vaccines as well as safe and effective adjuvants for humans, especially for immunocompromised people such as patients with diabetes mellitus. In this study, the protective effect of an MF59-adjuvanted inactivated whole-virion H5N1 vaccine was investigated in a type 1 diabetic mouse model. Mice (both healthy and diabetic) were immunized with a single dose of the inactivated vaccine, alone or adjuvanted with MF59 or Al(OH)(3). After four weeks, mice were challenged with a lethal dose of H5N1 virus. Antibody responses, survival rates, lung virus titers and body weight changes were tested. The results showed that addition of MF59 or Al(OH)(3) to the vaccine enhanced the antibody responses in both healthy mice and diabetic mice, but the MF59-adjuvanted groups showed higher antibody responses than the Al(OH)(3)-adjuvanted groups. The addition of MF59 or Al(OH)(3) to the vaccine led to a conversion of the immune response from a Th1-biased response to an enhanced mixed Th1/Th2 profile. The MF59-adjuvanted inactivated whole-virion H5N1 vaccine provided superior protection in type 1 diabetic mice to either the vaccine alone or the vaccine adjuvanted with Al(OH)(3).

닭 유래 아데노 바이러스 혈청형 4형(FAdV-4) 사독 오일 백신의 안전성 및 효능 평가

봉입체성 간염-심낭수종증(IBH-HPS)은 주로 육계에서 다발하며 3~6주령의 육계에서 최고 75%까지의 폐사율을 일으킬 수 있는 질병이다. 주 증상으로는 심낭의 황색 수양성 액체가 저류되는 심낭수종증과 함께 봉입체성 간염이 나타난다. 1987년 파키스탄에서 처음 발생이 보고된 후 여러 나라에서 발병되었으며, 최근 우리나라에서도 질병 발생이 확인된 바 있다. 본 실험에서는 IBH-HPS에 대한 경제적 피해를 감소시키기 위한 목적으로 사독 오일 백신을 제조하여 안전성 및 효능을 평가하였다. 2주령의 SPF 닭에 제조한 사독 백신을 1 또는 2수분으로 근육 접종한 뒤 2주 후인 4주령에 FAdV-4로 공격 접종을 실시하였다. 백신 접종에 의한 임상 증상 발현 및 폐사가 관찰되지 않아 백신의 안전성이 인정되었고, AGP 검사를 통해 FAdV-4에 대한 항체가 100% 형성되었음을 확인하였다. 공격 접종 시 각각 경구 또는 근육으로 접종하였고, 접종 후 10일간 관찰한 결과, 백신 접종군 모두 부검 소견, 바이러스 유전자 검색율 및 조직학적 병변도에 있어서 효능이 인정되었다. 육안 병변의 경우, 백신 비접종군에서는 간의 괴사 반점이 10~50%의 개체에서 발생한 데 비해 백신 접종군에서는 관찰되지 않았다. 바이러스 유전자 검색 양성률 또한 백신 접종군이 백신 비접종군에 비해 낮은 수준으로 나타났으며, 이는 특히 근육 투여군에서 더 명확하게 나타났다. 조직 병변도는 관찰 기간 내내 핵내 봉입체는 관찰되지 않았으나, 림프구 침윤 및 간세포의 괴사 정도가 백신 접종군에서 현저히 감소한 것을 확인할 수 있었다. 따라서, 본 실험에서 제조한 FAdV-4 사독 오일 백신은 실험계에 임상적으로 안전하고 면역원성도 높았으며, 효능에 있어서는 백신 비접종군에서의 임상 증상이 명확하지 않았음에도 불구하고, 육안 병변, 바이러스 검색율 및 조직 병변도에 있어서 공격 접종에 대한 방어가 효과적인 것으로 판단된다. Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) is an acute viral disease usually found in broilers aged from 3 to 5 weeks and causes up to 75% mortality. Among the 12 serotypes of fowl adenovirus group 1, serotype-4 (FAdV-4) was identified as a primary agent of IBH-HPS and was usually isolated in IBH-HPS cases in Korea since 2007. To prevent these IBH-HPS outbreaks in Korea, we developed the FAdV-4 inactivated vaccine using Korean isolate (ADL070244) and evaluated the efficacy of this vaccine. For the efficacy test, 2-week-old specific-pathogen-free (SPF) chickens intramuscularly inoculated with 1 or 2 dose of inactivated vaccine were used and challenged with FAdV-4 through either intramuscular or oral route at 2 weeks after vaccination. The vaccine induced good seroconversion which was confirmed by agar gel precipitation (AGP) test. In addition, the vaccine could decrease the FAdV-4 detection rate and histological lesion severity such as lymphocyte infiltration and necrosis in the liver comparing with those of non-vaccination group. Based on the current results, the developed FAdV-4 inactivated vaccine in this study was effective in the terms of reduction of virus detection rate and histological lesions severity. However, it was difficult to confirm the efficacy of the vaccine clearly because of no mortality and clinical signs in the non-vaccinated group after challenge. Therefore, we need further study to develop a standard challenged model system which could clearly evaluate the efficacy of the vaccines for FAdV-4.

Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity

In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX ®, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX ® [geometric mean titer (GMT) 20,480 vs. 1940, respectively ( P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX ® were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.

Experimental iron-inactivated Pasteurella multocida A: 1 vaccine adjuvanted with bacterial DNA is safe and protects chickens from fowl cholera

Fowl cholera is a serious problem in large and small scale poultry production. The present study describes the development and testing of an inactivated whole-cell, low-cost, safe, and effective vaccine for fowl cholera based on a previous work ( Vaccine 23:5590–5598). Pasteurella multocida A: 1 grown in the presence of low FeCl 3 concentrations, inactivated with higher concentrations of FeCl 3, and adjuvanted with bacterial DNA from P. multocida B: 2 containing immunostimulatory CpG motifs protect chickens with a lethal P. multocida A: 1 challenge. Chickens were immunized with two whole-cell inactivated vaccine doses at 4 weeks apart and challenged 4 weeks after booster immunization. Experimental vaccines were pure, easy injectable, and caused very little distress in chickens due to their aqueous consistency. Vaccines and bacterial DNA (bDNA) posed no safety problems when chickens were injected subcutaneously (s.c.) with a single, double, and overdose of these preparations. Immunized chickens produced systemic IgY antibodies (Ab) responses and vaccine adjuvanted with bDNA protected 100% chickens from lethal intrapertoneal (i.p.) P. multocida A: 1 challenge. This work suggests that use of bDNA as an adjuvant can improve the cost-effectiveness of inactivated veterinary vaccines for their use in developing countries. Our future studies will focus on safety and potency evaluation of experimental and current vaccines using bDNA as an adjuvant.

Long-term protective effect of post-exposure Havrix TM administration during viral hepatitis Type A outbreaks

Administration of human normal immunoglobulin (HNIG) post-exposure has been routinely used in Slovakia for outbreak control of hepatitis A, but requires deep intramuscular injection, provides only short-lived protection and is a human blood product. The protective effect of post-exposure administration of an inactivated hepatitis A vaccine was evaluated during 10 outbreaks in Slovakia. Direct contacts of confirmed hepatitis A cases received either: a single dose of hepatitis A vaccine (n = 2171) or immunoglobulin (HNIG, n = 3837). In the HNIG group the number of hepatitis A confirmed cases dropped within the first 7 weeks, however the decrease was not as rapid or as marked as that observed in the vaccinated group where the number of hepatitis A cases dropped within the first 4 weeks after vaccination. Among contacts, 67 cases of hepatitis A were detected during the maximum incubation period of 45 days: 16 cases (0.7%) in the vaccine group and 51 cases (1.3%) in the HNIG group (p < 0.05). After two and three years respectively, 50 and 39 volunteers who had previously received one dose of hepatitis A vaccine received a booster dose and anti-HAV antibodies were measured. Differences in anti-HAV antibody GMCs before and after the booster were statistically significant. The longer time interval (3 years instead of 2) between primary vaccination and booster administration did not seem to impact the magnitude of the booster response. The results of this study show that active post-exposure immunisation with only one dose of inactivated vaccine confers high and long-term protection and effectively controls viral hepatitis A outbreaks.

Optimisation of the inactivated vaccine dose against heartwater and in vitro quantification of Ehrlichia ruminantium challenge material

The aim of this work was to evaluate the minimal protective dose of the inactivated vaccine against heartwater. In order to conduct a reliable vaccination trial, an in vitro quantification method of Ehrlichia ruminantium ( ER) challenge doses was developed. In experimental conditions, homologous Gardel challenges with 2.1 × 10 4 to 9.4 × 10 4 live ER elementary bodies were reproducible and mimicked a natural challenge. Similar results were obtained when animals were challenged with 3 × 10 4 live elementary bodies from five different ER strains. A 28-fold reduction of the vaccine dose did not decrease protection when compared to the conventional dose of inactivated vaccine. Two injections of 35 μg of ER antigen induced good protection against heartwater. Moreover, we found that the amount of IFNγ secreted in blood from vaccinated animals after in vitro stimulation with ER antigen was not a reliable predictor of survival and could not be used to test the potency of the inactivated vaccine.

Tiered Use of Inactivated Influenza Vaccine in the Event of a Vaccine Shortage

The United States has experienced disruptions in the manufacture or distribution of inactivated influenza vaccine during three of the last five influenza seasons. Delays in delivery of influenza vaccine or vaccine shortages remain possible, in part, because of inherent time constraints in manufacturing the vaccine, given the annual updating of influenza vaccine strains and uncertainties regarding vaccine supply (including licensure of new vaccine preparations). Although total vaccine supply for the 2005-06 influenza season is not yet known, the minimum anticipated supply is approximately 58-60 million doses of inactivated vaccine and 3 million doses of live, attenuated vaccine. This estimated supply is similar to that available during the 2004-05 season and would be adequate to satisfy historical demand for influenza vaccine among persons considered by the Advisory Committee on Immunization Practices (ACIP) to be at high risk for serious complications associated with influenza virus infection, health-care workers, and household contacts of children aged <6 months. These groups were prioritized for influenza vaccination in 2004-05. Additional doses of inactivated influenza vaccine might be available for the U.S. market in 2005-06, but this cannot yet be confirmed. Availability of additional vaccine would allow for expansion of the priority groups and, preferably, vaccination of all persons who desire it.

Epidemiological Situation of Japanese Encephalitis in Nepal

A human Japanese encephalitis (JE) case is considered to have elevated temperature (over 380 C) along with altered consciousness or unconsciousness and is generally confirmed serologically by finding of specific anti-JE IgM in the cerebro spinal fluid. No specific treatment for JE is available. Only supportive treatment like meticulous nursing care, introduction of Ryle's tube if the patient is unconscious, dextrose solution if dehydration is present, manitol injection in case of raised cranial temperature and diazepam in case of convulsion. Intra venous fluids, indwelling catheter in conscious patient and corticosteroids unless indicated should be avoided. Pigs, wading birds and ducks have been incriminated as important vertebrate amplifying hosts for JE virus due to viremia in them. Man along with bovines, ovines and caprines is involved in transmission cycle as accidental hosts and plays no role in perpetuating the virus due to the lack of viremia in them. The species Cx tritaeniorhyncus is suspected to be the principal vector of JE in Nepal as the species is abundantly found in the rice-field ecosystem of the endemic areas during the transmission season and JE virus isolates have been obtained from a pool of Cx tritaeniorhyncus females. Mosquito vector become infective 14 days after acquiring the JR virus from the viremic host. The disease was first recorded in Nepal in 1978 as an epidemic in Rupandehi district of the Western Development Region (WDR) and Morang of the Eastern Region (EDR). At present the disease is endemic in 24 districts. Although JE as found endemic mainly in tropical climate areas, existence and proliferation of encephalitis causing viruses in temperate and cold climates of hills and valleys are possible. Total of 26,667 cases and 5,381 deaths have been reported with average case fatality rate of 20.2% in an aggregate since 1978. More than 50% of morbidity and 60% mortality occur in the age group below 15 years. Upsurge of cases take place after the rainy season (monsoon). Cases start to appear in the month of April - May and reach its peak during late August to early September and start to decline from October. There are four designated referral laboratories, namely National Public Health Laboratory (Teku), Vector Borne Diseases Research and Training Center (Hetauda), B.P. Koirala Institute of Medical Sciences (Dharan) and JE Laboratory (Nepalgunj), for confirmatory diagnosis of JE. For prevention of JE infection; chemical and biological control of vectors including environmental management at breeding sites are necessary. Segregate pigs from humans habitation. Wear long sleeved clothes and trousers and use repellent and bed net to avoid exposure to mosquitos. For the prevention of the disease in humans, safe and efficacious vaccines are available. Therefore immunize population at risk against JE. Immunize pigs at the surroundings against JE. 225,000 doses of live attenuated SA-14-14.2 JE vaccine were received in donation from Boran Pharmaceuticals, South Korea for the first time in Nepal. Altogether 224,000 children aged between 1 to 15 years were vaccinated in Banke, Bardiya and Kailali districts during 1999. From China also, 2,000,000 doses of inactivated vaccine were received in 2000 and a total of 481,421 children aged between 6m to 10 yrs were protected from JE during 2001/2002. Ministry of Agriculture, Department of Livestock Services has vaccinated around 200,000 pigs against JE in terai zone during February 2001.

Evaluation of a single dose of half strength inactivated influenza vaccine in healthy adults

Because of delays in the manufacturing of the 2000–2001, trivalent inactivated influenza vaccine in the US, there were concerns that there might be shortages of vaccine supply in the US. Therefore, we conducted a prospective, randomized, open-label, multicenter trial at six academic medical centers in the US, to evaluate the immunogenicity of a half dose of inactivated vaccine in healthy adults. Healthy adults between the ages of 18 and 49 were randomized to receive either a full 0.5 ml (15.5 μg of each HA antigen) dose or a 0.25 ml (7.75 μg of each HA antigen) dose of the 2000–2001 trivalent inactivated influenza vaccine by intramuscular injection. Sera were obtained for assessment of hemagglutination-inhibiting antibody to each of the three strains contained in the vaccine before and 21 days after vaccination. The proportions of individuals achieving a post-vaccination titer of ≥1:40, the geometric mean titers (GMTs) of post-vaccination antibody, and the proportions of individuals with a four-fold or greater increase in antibody were lower for all three strains in those receiving 0.25 ml of vaccine compared to those receiving 0.5 ml. However, the differences were small for all three antigens. The upper 95% confidence limits for differences between 0.25 and 0.5 ml doses were less than 20% for rates of achieving a titer of ≥1:40 and four-fold response, and less than 1.5 for the ratios of GMTs between dose groups, for all three vaccine antigens. These results suggest that when vaccine is in short supply, a strategy using a half dose in healthy adults could increase the number of people vaccinated with relatively little adverse impact on vaccine immunogenicity.

Primary and booster immune responses to SA14-14-2 Japanese encephalitis vaccine in Korean infants

Attenuated SA14-14-2 Japanese encephalitis (JE) vaccine has been administered safely and effectively to more than 100 million children in China since 1988 and recently, licensure of the vaccine in Korea has been sought. In the first clinical evaluation of the vaccine outside of China, we monitored side effects in 84 children and evaluated antibody responses to a single dose given as primary JE vaccination in 68 children, 1–3 years old (mean age 27 months). No significant adverse events were noted. Neutralizing antibodies (geometric mean titer [GMT] of 188) were produced in 96% of the 68 subjects. In 10 other children who previously had been immunized with two or three doses of inactivated JE vaccine, the booster administration of SA14-14-2 vaccine produced an anamnestic response in all, with a GMT of 3378. In a comparison group of 25 children previously immunized with two doses of inactivated vaccine, neutralizing antibody titers were detected in 16 (64%). Viral specific IgM was detected in nine primary vaccinees (13%) but in others, IgM may have declined to undetectable levels in the four week postimmunization sample. Live attenuated SA14-14-2 JE vaccine is a promising alternative to the only commercially available JE vaccine for national childhood immunization programs in Asia.

Maternal transfer of paramyxovirus type 1 antibodies and antibody response to a live Newcastle disease vaccine in kori bustards.

Studies were conducted to monitor the decline of maternal antibodies to paramyxovirus type 1 (PMV-1) in kori bustard chicks (Ardeotis kori), and to determine the antibody response in birds with low levels of maternally derived immunity (MDI) after being given either one or five times the standard domestic fowl dose of a live PMV-1 La Sota vaccine intranasally. The results confirmed that PMV-1 antibodies were transferred to eggs and chicks derived from kori bustard hens immunized with inactivated vaccine 5 to 8 mo previously. The levels of inherited antibody in chicks varied considerably, with 21% of birds having no detectable antibodies at day 14 Chicks hatched from dams with high hemagglutination inhibition (HI) antibody titers had high titers of MDI. Mean antibody levels in seropositive chicks were log2 6.3 and log2 2.9 on days 14 and 42, respectively. The rate of decline of detectable antibodies (1 log2), was estimated to be 5.50 to 6.25 days and 12.25 days in 14 to 21 and 28 to 42 day old chicks, respectively. There was no significant HI antibody response in bustards given a primary vaccination of either one or five times the standard domestic fowl dose of live vaccine intranasally up to 3 wk post-vaccination. High levels of HI antibodies, log2 7.4, were detected in birds given a secondary dose of inactivated vaccine, but not in birds given a secondary dose of live vaccine at 2 wk post-vaccination.

Studies with inactivated duck virus hepatitis vaccines in breeder ducks

Inactivated duck virus hepatitis (DVH) oil emulsion vaccines were prepared and evaluated in White Pekin breeder ducks and compared to a live DVH vaccine obtained from a commercial source. The response to vaccination was measured by serum neutralisation (SN) tests and resistance to experimental challenge in ducklings bred from vaccinated parents 32-35 weeks of age. Inactivated vaccines prepared from DVH virus grown in duck eggs stimulated a better antibody response than vaccines prepared from virus grown in chicken eggs. This was probably due to the higher yield of virus obtained from the duck eggs. Neither inactivated vaccine produced a satisfactory antibody response when used as a primary vaccine in 16-week-old ducks. Using the inactivated vaccine prepared from virus grown in duck eggs an improved antibody response was recorded when the vaccine was given in three doses at 8, 16 and 22 weeks of age. The levels of antibody in the breeding ducks was sufficiently high to confer protection to their progeny for up to 3 weeks of age. Ducks vaccinated at 2-3 days of age with the live DVH vaccine produced a high and sustained antibody response for up to 30 weeks. Ducklings bred from this group were resistant to challenge for up to 3 weeks of age. Ducks that were given live DVH vaccine at 2-3 days of age followed by inactivated vaccine at 22 weeks of age produced SN antibody levels significantly higher than levels produced from three doses of inactivated vaccine or one dose of live vaccine. Ducklings bred from these ducks were resistant to challenge for up to 3 weeks of age. These results suggest that inactivated DVH vaccines may be of value where the use of live DVH vaccines are contra-indicated.

The geography of neurology.

<h3>Abstract</h3> The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the host’s molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.

Measles vaccination. VII. Follow-up studies in children immunized with four doses of inactivated vaccine.

SummaryChildren immunized with 4 doses of formalin‐killed (FK) whole virus vaccine containing adjuvant and aqueous, purified hemagglutinin prepared from Tween‐ether (TE) treated material in different combinations have been followed serologically and clinically during a period of 3 to 4 years after the last dose of vaccine. The average decline in HI antibody titers was about 10‐fold during this period of time, except in children who had received 4 doses of TE vaccine. The latter group displayed about a 40‐fold decrease in titers. Four out of 10 children exposed to cases of regular measles displayed clinical symptoms of varying degrees of severity. Two more children responded with a rise in HI antibody titer only. All these reactions occurred in children with a pre‐exposure HI serum titer of 160 or higher. A case of pneumonia was encountered in connection with exposure to wild virus in a child who had received only 2 doses of FK vaccine.

MEASLES IMMUNIZATION INCORPORATED IN THE ROUTINE SCHEDULE FOR INFANTS: EFFICACY OF A COMBINED INACTIVATED-LIVE VACCINATION REGIMEN

1. Live attenuated measles virus vaccine without gamma globulin was extremely well tolerated by infants 12 to 14 months of age if they received 3 doses of inactivated vaccine at about 2, 3, and 4 months of age. This phenomenon was observed in spite of no detectable antibody after inactivated vaccine and a consistent antibody response after live vaccine. 2. Three inoculations of inactivated vaccine appeared to have an attenuating effect on measles infection acquired within 9 months by 17 infants; at least 70% of these infants were proved to have a subclinical disease by serologic studies. 3. The failure to detect antibody following three inoculations of killed vaccine probably reflects the lack of sensitivity of the HI antibody test which was employed in this study. The attenuating effect of the killed vaccine on the natural disease and on the measles vaccine-virus disease provides indirect evidence of antibody formation. 4. If killed measles vaccine can be successfully incorporated with diphtheriapertussis-tetanus toxoid it should be a useful preparation for primary immunization during the first 6 months of life. However, it would be most important to complete the immunization with an inoculation of live attenuated measles-virus vaccine at 12 to 14 months of age.

Poliomyelitis-Newberry County, South Carolina, 1961. A break with the past.

In 1961, Newberry County, South Carolina, reported more clinically recognized cases of poliomyelitis than ever before noted in that area. A total of 24 cases caused by Type 3 poliomyelitis virus were recognized; the rate of attack for the country was 83 per 100,000 persons. The epidemiological pattern of age and race involvement in this outbreak differed from previous experiences with poliomyelitis in South Carolina in that Negro children of school age were predominantly involved. It is suggested that personal contact through the Negro elementary school was a major factor in viral spread. The extent to which inactivated (Salk) poliomyelitis vaccine had been used varied between the Negro and other segments of the community. Only 2 of the 24 patients involved had received as many as 3 doses of inactivated vaccine.