Effectiveness of quadrivalent HPV vaccination in reducing vaccine-type and nonvaccine-type high risk HPV infection.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

Diversity of amino acid substitutions of penicillin-binding proteins in penicillin-non-susceptible and non-vaccine type Streptococcus pneumoniae.

PURPOSE: In Japan, the introduction of pneumococcal conjugate vaccine (PCV) in children has decreased vaccine-type (VT) pneumococcal infections caused by penicillin (PEN)-non-susceptible Streptococcus pneumoniae. PEN-non-susceptible strains have gradually emerged among non-vaccine types (NVT). In this study, we aim to investigate the pbp gene mutations and the characteristics of PEN-binding proteins (PBPs) that mediate PEN resistance in NVT strains. MATERIALS AND METHODS: Pneumococcal 41 strains of NVT isolated from patients with invasive pneumococcal infection were randomly selected. Nucleotide sequences for pbp genes encoding PBP1A, PBP2X, and PBP2B were analyzed, and amino acid (AA) substitutions that contribute to ß-lactam resistance were identified. In addition, the three-dimensional (3D) structure of abnormal PBPs in the resistant strain was compared with that of a reference R6 strain via homology modeling. RESULTS: In PEN-non-susceptible NVT strains, Thr to Ala or Ser substitutions in the conserved AA motif (STMK) were important in PBP1A and PBP2X. In PBP2B, substitutions from Thr to Ala, adjacent to the SSN motif, and from Glu to Gly were essential. The 3D structure modeling indicated that AA substitutions are characterized by accumulation around the enzymatic active pocket in PBPs. Many AA substitutions detected throughout the PBP domains were not associated with resistance, except for AA substitutions in or adjacent to AA motifs. Clonal complexes and sequence types showed that almost all NVT cases originated in other countries and spread to Japan via repeat mutations. CONCLUSIONS: NVT with diverse AA substitutions increased gradually with pressure from both antimicrobial agents and vaccines.

Reduced Influenza B-Specific Postvaccination Antibody Cross-reactivity in the B/Victoria Lineage-Predominant 2019/20 Season.

BACKGROUND: The influenza activity of the 2019/20 season remained high and widespread in the United States with type B viruses predominating the early season. The majority of B viruses characterized belonged to B/Victoria (B/Vic) lineage and contained a triple deletion of amino acid (aa) 162-164 in hemagglutinin (3DEL). These 3DEL viruses are antigenically distinct from B/Colorado/06/2017 (CO/06)-the B/Vic vaccine component of the 2018/19 and 2019/20 seasons representing the viruses with a double deletion of aa 162-163 in hemagglutinin (2DEL). METHODS: We performed molecular characterization and phylogenetic analysis of circulating B/Vic viruses. We also conducted hemagglutination inhibition (HAI) assay using archived human postvaccination sera collected from healthy subjects administered with different types of 2018/19 or 2019/20 seasonal vaccines. Their HAI cross-reactivity to representative 3DEL viruses was analyzed. RESULTS: The CO/06-specific human postvaccination sera, after being adjusted for vaccine type, had significantly reduced HAI cross-reactivity toward representative 3DEL viruses, especially the 136E+150K subgroup. The geometric mean titers against 3DEL viruses containing 136E+150K mutations were 1.6-fold lower in all populations (P = .051) and 1.9-fold lower in adults (P = .016) compared with those against the 136E+150N viruses. CONCLUSIONS: Our results indicate that postvaccination antibodies induced by the B/Vic vaccine component of the 2019/20 influenza season had reduced HAI cross-reactivity toward predominant 3DEL viruses in the United States. A close monitoring of the 3DEL 136E+150K subgroup is warranted should this subgroup return and predominate the 2020/21 influenza season.

Meta-analysis of antiviral protection of white spot syndrome virus vaccine to the shrimp.

Currently, white spot syndrome virus (WSSV) is one of the most serious pathogens that impacts shrimp farming around the world. A WSSV vaccine provides a significant protective benefit to the host shrimp. Although various types of vaccines against WSSV have emerged, the immune effects among them were not compared, and it remains unclear which type of vaccine has the strongest protective effect. Meanwhile, due to the lack of effective routes of administration and immunization programs, WSSV vaccines have been greatly limited in the actual shrimp farming. To answer these questions, this study conducted a comprehensive meta-analysis over dozens of studies and compared all types WSSV vaccines, which include sub-unit protein vaccines, whole virus inactivated vaccines, DNA vaccines and RNA-based vaccines. The results showed that the RNA-based vaccine had the highest protection rate over the other three types of vaccines. Among the various sub-unit protein vaccines, VP26 vaccine had the best protective effects than other sub-unit protein vaccines. Moreover, this study demonstrated that vaccines expressed in eukaryotic hosts had higher protection rates than that of prokaryotic systems. Among the three immunization modes (oral administration, immersion and injection) used in monovalent protein vaccines, oral administration had the highest protection rate. In natural conditions, shrimp are mostly infected by the virus orally. These results provide a guide for exploration of a novel WSSV vaccine and help facilitate the application of WSSV vaccines in shrimp farming.

Experiences and lessons learned from 29 HPV vaccination programs implemented in 19 low and middle-income countries, 2009-2014.

BACKGROUND: Cervical cancer is the greatest cause of age-weighted years of life lost in the developing world. Human papillomavirus (HPV) infection is associated with a high proportion of cervical cancers, and HPV vaccination may help to reduce the incidence of cancer. The aim of the study was to identify barriers, obstacles, and strategies and to analyze key concerns and lessons learned with respect to the implementation of HPV vaccination program in low- and middle-income countries. METHODS: The Gardasil Access Program (GAP) is a donation program established to enable organizations and institutions in eligible low-resource countries to gain operational experience designing and implementing HPV vaccination programs. This study used an online survey to capture the experiences and insights of program managers participating in the GAP. Different factors related to HPV vaccination program management were collected. A mixed-method approach enabled the presentation of both quantitative measurements and qualitative insights. RESULTS: Twenty-nine programs implemented by 23 institutions in 19 low- and middle-income countries were included. Twenty programs managers (97.7 %) reported that their institution implemented sensitization strategies about vaccination prior to the launch of vaccination campaign. The most frequently reported obstacles to HPV vaccination by the program managers were erroneous perceptions of population related to the vaccine's safety and efficacy. Reaching and maintaining follow-up with target populations were identified as challenges. Insufficient infrastructure and human resources financing and the vaccine delivery method were identified as significant health system barriers. Coupling HPV vaccination with other health interventions for mothers of targeted girls helped to increase vaccination and cervical cancer screening. The majority of program managers reported that their programs had a positive impact on national HPV vaccination policy. The majority of institutions had national and international partners that provided support for human resources, technical assistance, and training and financial support for health professionals. CONCLUSION: Local organizations and institutions can implement successful HPV vaccination campaigns. Adequate and adapted planning and resources that support information sharing, sensitization, and mobilization are essential for such success. These results can inform the development of programs and policies related to HPV vaccination in low- and middle-income countries.

Safety of incidental exposure to the novel oral poliovirus vaccine type 2 in pregnancy: A longitudinal observational study in Mozambique, 2022-2023.

BACKGROUND: To minimize the risk of vaccine-derived poliovirus emergences, the novel oral poliovirus vaccine type 2 (nOPV2), was bioengineered to have increased genetic stability compared to Sabin OPV and recommended for outbreak response Emergency Use Listing by WHO. Although pregnant women are not a target population for this vaccine, a theoretical risk of incidental exposure exists via pharyngeal or faecal shedding from vaccinated children in the household or close community. METHODS: This was an observational study of pregnant women conducted in Nampula (exposed cohort) and Maputo (non-exposed cohort) in Mozambique from August 2022 to June 2023. Two nOPV2 campaigns were conducted in Nampula and none in Maputo. Women were followed-up during routine prenatal consultation, delivery, and 28-day neonate visits for obstetric anomalies and pregnancy outcomes. Sociodemographic, medical, and obstetric history was captured. RESULTS: Three hundred twenty-six pregnant women were enrolled from Nampula and 940 from Maputo City. Stillbirth prevalence (2·3% vs 1·6%, p = 0·438), low birth weight (8·9% vs 8·2%, p = 0·989), congenital anomalies (1 % vs 0·5%, p = 0·454), neonatal death (2·3% vs 1·6%, p = 0·08), and maternal death (0 % vs 0·2%, p = 0·978) did not differ amongst exposed and non-exposed cohorts. There was an increased rate of pre-term delivery in the exposed cohort (18·4% vs 11·0%, p = 0·011). CONCLUSION: We did not observe an increased frequency of adverse pregnancy outcomes due to passive nOPV2 exposure. A higher frequency of preterm delivery needs to be further investigated. The data reported herein support the continued use of nOPV2 for poliovirus outbreak response and full licensure of the vaccine.

Detection of Polioviruses Type 2 among Migrant Children Arriving to the Russian Federation from a Country with a Registered Poliomyelitis Outbreak.

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021-April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being.

Laboratory response to an infant with suspected measles vaccine associated fever and rash in Sri Lanka.

Background: Measles is a highly contagious illness. Sri Lanka (SL) has eliminated the measles in 2019. The country is at risk of importation of measles and there could be vaccine-associated measles like illnesses. Therefore, it is important to investigate patients with fever, rash to differentiate the wild-type from vaccine-type excluding other suspected pathogens to direct infection prevention and control strategies. The objective is to describe the laboratory investigation procedure in an immunocompetent child, developed fever, rash following measles containing vaccine in post-measles eliminated period, SL. Methods: This laboratory based investigation was carried out in National Measles Laboratory, SL. Blood and throat swab were received from a patient with fever, rash, cough and coryza developed at tenth day of receiving the measles containing live-attenuated vaccine. Samples were tested for measles, rubella, and other relevant pathogens according to the laboratory testing algorithm for an immunocompetent child with fever, rash and flu like symptoms. Results: Measles vaccine type A, Edmonston-strain virus was detected after sequencing in throat swab and measles IgM and IgG were positive at sixth-week of illness-onset. In addition, influenza A RNA was detected in throat swab at day-three with detectable parvoB19 IgM in blood sample received at sixth-week of post-onset symptoms. Conclusions: Measles like illness of this immunocompetent child who received measles containing vaccine could be due to measles vaccine-type A or influenza infection. In a measles eliminated, resource-limited setting in SL, there should be a well-defined, testing algorithm to exclude prevalent possible pathogens according to epidemiological and clinical information.

COVID-19 in early 2023: Structure, replication mechanism, variants of SARS-CoV-2, diagnostic tests, and vaccine & drug development studies.

Coronavirus Disease-19 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome-coronaviruses-2 (SARS-CoV-2), a highly pathogenic and transmissible coronavirus. Most cases of COVID-19 have mild to moderate symptoms, including cough, fever, myalgias, and headache. On the other hand, this coronavirus can lead to severe complications and death in some cases. Therefore, vaccination is the most effective tool to prevent and eradicate COVID-19 disease. Also, rapid and effective diagnostic tests are critical in identifying cases of COVID-19. The COVID-19 pandemic has a dynamic structure on the agenda and contains up-to-date developments. This article has comprehensively discussed the most up-to-date pandemic situation since it first appeared. For the first time, not only the structure, replication mechanism, and variants of SARS-CoV-2 (Alpha, Beta, Gamma, Omicron, Delta, Epsilon, Kappa, Mu, Eta, Zeta, Theta, lota, Lambda) but also all the details of the pandemic, such as how it came out, how it spread, current cases, what precautions should be taken, prevention strategies, the vaccines produced, the tests developed, and the drugs used are reviewed in every aspect. Herein, the comparison of diagnostic tests for SARS-CoV-2 in terms of procedure, accuracy, cost, and time has been presented. The mechanism, safety, efficacy, and effectiveness of COVID-19 vaccines against SARS-CoV-2 variants have been evaluated. Drug studies, therapeutic targets, various immunomodulators, and antiviral molecules applied to patients with COVID-19 have been reviewed.

Implementing a robust adverse event of special interest surveillance for novel oral polio vaccine type 2 rollout, Nigeria, March-July 2021.

Introduction: novel oral poliovirus vaccine type 2 (nOPV2), designed to be more genetically stable than Sabin-strain oral poliovirus vaccine type 2 (mOPV2), is a new and key component of the Global Polio Eradication Initiative's strategy to combat outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2). The World Health Organization´s (WHO´s) emergency use listing (EUL) requires extensive safety monitoring for Adverse Event of Special Interest (AESI) in its use. We implemented AESI active surveillance to monitor the safety of the nOPV2 in Nigeria. Methods: a cross-sectional assessment was conducted in Nigeria during March-June 2021 in 117 local government areas (LGAs) across 6 states and the Federal Capital Area with confirmed cVDPV2 transmission. We conducted active searches for nOPV2 AESI in all health facilities. Suspected events were ascertained, and vaccination and clinical data abstracted. Events were classified using WHO causality assessment algorithm. Data were analyzed using Epi info7. Results: total of 234 adverse events were reported after 21,997,300 doses of nOPV2 were administered, giving a crude reported incidence of 1 in 94,000 doses of nOPV2. Altogether, 221 of the 234 (94%) adverse events were classified. For 166 AESI ascertained to occur following a dose of nOPV2, the corrected crude incidence rate was 1 in 133,000 doses; 4 of the adverse events, were classified as consistent with casual association with nOPV2 vaccination. Conclusion: we found that nOPV2 had a low incidence of AESI following nOPV2 campaigns and no new or unexpected adverse event was reported. Safety monitoring should be sustained for early detection of signals and uncommon adverse events.

Preference for human papillomavirus vaccine type and vaccination strategy among parents of school-age girls in Guangdong province, China.

In China, the human papillomavirus (HPV) vaccination coverage among age-eligible girls is rather low, and parent's attitude often plays a determinant role in their girls' HPV vaccination. To accelerate HPV vaccination coverage, several cities and Guangdong province in China offered different HPV vaccine types with different reimbursement methods. In April 2022, we conducted a province-wide survey to investigate parents of children aged 9-15 in Guangdong province, and analyzed factors associated with their preference for HPV vaccine type and vaccination strategy. Of the 4,967 surveyed respondents, 2,610 (58.1%) have not yet vaccinated their children. Among these parents, 67.9% preferred to vaccinate their children with the nine-valent vaccine, while only 8.1% preferred the quadrivalent vaccine and 7.4% preferred the bivalent vaccine. More parents preferred fixed subsidies with free choices of HPV vaccine type over the domestic bivalent vaccine provided by the government (58.1% vs. 39.3%). The multinomial logistic regression showed that parents' relationship with children, educational level, household income, and vaccination status were significantly associated with parents' preference for HPV vaccine type. Parent's relationship with children, workplace, household income, vaccination status, and age of children, were significantly associated with parents' preference for HPV vaccination strategy. Our findings suggest that policymakers may consider adjusting the current vaccination strategy by offering more vaccination choices. More health education on HPV vaccine and vaccination should also be provided to parents of age-eligible girls. Future research should examine which HPV vaccination strategy is more effective in promoting HPV vaccine uptakes in China.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

The impact of vaccination on the burden of invasive pneumococcal disease from a nationwide surveillance program in Lebanon: an unexpected increase in mortality driven by non-vaccine serotypes.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on the burden of invasive pneumococcal disease (IPD) and serotype distribution was examined across age groups from data collected by the Lebanese Inter-Hospital Pneumococcal Surveillance Program. METHODS: Between 2005 and 2020, 593 invasive Streptococcus pneumoniae isolates were collected from 79 hospitals throughout Lebanon. Serotypes and antimicrobial resistance (AMR) profiles were identified, and trends compared over 3 eras: PCV7, post-PCV7/ pre-PCV13, and PCV13 eras. RESULTS: The prevalence of PCV7 serotypes decreased significantly from 43.6% in the PCV7 era to 17.8% during the PCV13 era (p<0.001). PCV13-only serotypes remained stable in the PCV13 compared to the post-PCV7 eras, especially serotypes 1 and 3, whereas non-vaccine types (NVT) increased throughout the study period, especially 24 and 16F. The mortality rate increased substantially from 12.5% (PCV7 era) to 24.8% (PCV13 era). A significant decrease in AMR was observed across the three study eras. CONCLUSION: PCVs substantially impacted IPD and AMR in vaccinated and unvaccinated populations despite an increase in mortality driven by NVT. Broadening the recommendation of vaccination to include older age-groups, using higher valency vaccines, and implementing stringent antimicrobial stewardship are likely to further impact the burden of IPD.

Comprehensive narrative review of real-world COVID-19 vaccines: viewpoints and opportunities.

Currently, people all over the world have been affected by coronavirus disease 2019 (COVID-19). Fighting against COVID-19 is the top priority for all the countries and nations. The development of a safe and effective COVID-19 vaccine is considered the optimal way of ending the pandemic. Three hundred and 44 vaccines were in development, with 149 undergoing clinical research and 35 authorized for emergency use as to March 15 of 2022. Many studies have shown the effective role of COVID-19 vaccines in preventing SARS-CoV-2 infections as well as serious and fatal COVID-19 cases. However, tough challenges have arisen regarding COVID-19 vaccines, including long-term immunity, emerging COVID-19 variants, and vaccine inequalities. A systematic review was performed of recent COVID-19 vaccine studies, with a focus on vaccine type, efficacy and effectiveness, and protection against SARS-CoV-2 variants, breakthrough infections, safety, deployment and vaccine strategies used in the real-world. Ultimately, there is a need to establish a unified evaluation standard of vaccine effectiveness, monitor vaccine safety and effectiveness, along with the virological characteristics of SARS-CoV-2 variants; and determine the most useful booster schedule. These aspects must be coordinated to ensure timely responses to beneficial or detrimental situations. In the future, global efforts should be directed toward effective and immediate vaccine allocations, improving vaccine coverage, SARS-CoV-2 new variants tracking, and vaccine booster development.

Research status and perspectives for pathogenic spirochete vaccines.

Leptospira interrogans, Borrelia burgdorferi, and Treponema pallidum are important pathogenic spirochetes. The incidence of human diseases caused by pathogenic spirochetes, e.g., leptospirosis, Lyme disease, and syphilis, has been recently increased, posing a threat to public health. Mechanisms of spirochete pathogenicity are not yet fully understood, and no safe and effective vaccine to prevent and control the infection by pathogenic spirochetes is currently available. In this article, we review the progress of research into the pathogenic spirochete vaccine, mainly in terms of vaccine types. The development of relevant vaccines against pathogenic spirochetes has generally proceeded via several stages, such as the whole-cell inactivated vaccine, live attenuated vaccine, and gene-engineered vaccine, and will likely enter a new stage with the application of gene editing technology. In this review, we mainly summarized the types of pathogenic spirochete vaccines and conducted a preliminary analysis on the protective effect of immunity, and proposed a further prospect for the development of pathogenic spirochete vaccines.

Impact of the introduction of a 13-valent pneumococcal vaccine on pneumococcal serotypes in non-invasive isolates from 2007 to 2016 at a teaching hospital in Japan.

PURPOSE: To prevent severe invasive pneumococcal infection, pneumococcal conjugate vaccines (PCVs) were introduced in Japan in 2010, and in 2013 a pneumococcal 13-valent conjugate vaccine (PCV13) was included in the routine vaccination schedule for infants. In this study, we analysed the antimicrobial susceptibilities and capsular types of pneumococci isolated from non-invasive patient sites from 2007 to 2016 to assess the impact of the introduction of PCV13. METHODOLOGY: A total of 618 pneumococcal isolates collected at a teaching hospital from 2007 to 2016 were used. These isolates were characterized by capsular typing, multilocus sequence typing and antimicrobial susceptibility testing. RESULTS: Capsular typing indicated that, after the introduction of the PCV, the proportion of PCV13 serotypes decreased (P<0.01), while non-PCV13 serotypes became diverse. In particular, increases in 22 F, 15A and 23A were noted among non-PCV13 serotypes. Regarding antimicrobial susceptibility, the non-susceptibility rate to penicillin of pneumococci that showed higher minimum inhibitory concentrations (MICs) than the susceptibility breakpoint decreased, and pneumococci tended to become susceptible. However, all type 23A pneumococci and 77.8  % of type 15A pneumococci showed the reverse trend, with low susceptibility to penicillin. Furthermore, all 15A and 23A isolates had macrolide resistance genes. CONCLUSION: These data suggest that PCVs can prevent infections caused by PCV serotypes. However, since non-PCV13-type pneumococci, in particular 15A and 23A, which have acquired multidrug resistance, have already emerged over time, the development of a novel vaccine targeting a broader spectrum of pneumococci is warranted.

Antigen delivery format variation and formulation stability through use of a hybrid vector.

A hybrid biological-biomaterial antigen delivery vector comprised of a polymeric shell encapsulating an Escherichia coli core was previously developed for in situ antigen production and subsequent delivery. Due to the engineering capacity of the bacterial core, the hybrid vector provides unique opportunities for immunogenicity optimization through varying cellular localization (cytoplasm, periplasm, cellular surface) and type (protein or DNA) of antigen. In this work, three protein-based hybrid vector formats were compared in which the pneumococcal surface protein A (PspA) was localized to the cytoplasm, surface, and periplasmic space of the bacterial core for vaccination against pneumococcal disease. Furthermore, we tested the hybrid vector's capacity as a DNA vaccine against Streptococcus pneumoniae by introducing a plasmid into the bacterial core to facilitate PspA expression in antigen presenting cells (APCs). Through testing these various formulations, we determined that cytoplasmic accumulation of PspA elicited the strongest immune response (antibody production and protection against bacterial challenge) and enabled complete protection at substantially lower doses when compared to vaccination with PspA + adjuvant. We also improved the storage stability of the hybrid vector to retain complete activity after 1 month at 4 °C using an approach in which hybrid vectors suspended in a microbial freeze drying buffer were desiccated. These results demonstrate the flexibility and robustness of the hybrid vector formulation, which has the potential to be a potent vaccine against S. pneumoniae.

Progress of Middle East respiratory syndrome coronavirus vaccines: a patent review.

INTRODUCTION: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a new pathogen, causing severe complications and a high case fatality rate. No direct treatments are available as yet, highlighting the importance of prevention through suitable vaccination regimes. The viral spike (S) protein has been characterized as a key target antigen for vaccines. In particular, S protein domains have been utilized to produce high titers of neutralizing antibodies. Areas covered: Since the first report of MERS-CoV infection, a limited number of MERS-CoV-specific patents have been filed. Patents related to MERS-CoV are categorized into three areas: treatments, antibodies, and vaccines (receptor-related). This review mainly focuses on the types and efficacies of vaccines, briefly covering treatments and antibodies against the virus. MERS-CoV vaccine forms and delivery systems, together with comparable development strategies against SARS-CoV are additionally addressed. Expert opinion: Vaccines must be combined with delivery systems, administration routes, and adjuvants to maximize T-cell responses as well as neutralizing antibody production. High immune responses require further study in animal models, such as human receptor-expressing mice, non-human primates, and camels. Such a consideration of integrated actions should contribute to the rapid development of vaccines against MERS-CoV and related coronaviruses.

Effect on nasopharyngeal pneumococcal carriage of replacing PCV7 with PCV13 in the Expanded Programme of Immunization in The Gambia.

INTRODUCTION: In 2011, two years after the introduction of 7-valent Pneumococcal conjugate vaccine (PCV7), the Gambian immunization programme replaced PVC7 with PCV13 (13-valent). Our objective was to assess the additional impact of PCV13 on prevalence of pneumococcal nasopharyngeal carriage. METHODS: We recruited healthy Gambian infants who had received three PCV doses. Nasopharyngeal swabs were collected from infants and their mothers during two cross-sectional surveys (CSS) conducted in infants vaccinated with PCV7 (CSS1) and vaccinated with PCV13 (CSS2). Pneumococci were isolated and serotyped following standardized methods. Whole genome sequencing was performed on non-typable pneumococcus isolated in CSS1 and CSS2. RESULTS: 339 and 350 infants and their mothers were recruited in CSS1 and CSS2, respectively. Overall prevalence of pneumococcal carriage was 85.4% in infants. Among infants, prevalence of vaccine type (VT) carriage was lower in CSS2 [9.4% versus 4.9% (p=0.025) for PCV7-VT; 33.3% versus 18.3% (p<0.001) for PCV13-VT and 23.9% versus 13.7% (p=0.001) for the 6 additional serotypes included in PCV13]. At CSS2, there was a decrease of serotypes 6A (from 15.3% to 5.7%, p<0.001) and 19F (from 5.6% to 1.7%, p=0.007), and an increase of non-typable pneumococci (0.3-6.0%, p<0.001), most of which (82.4%) were from typable serotype backgrounds that had lost the ability to express a capsule. Prevalence of overall and VT carriage in mothers was similar in CSS1 and CSS2. CONCLUSIONS: Replacing PCV7 for PCV13 rapidly decreased prevalence of VT carriage among vaccinated Gambian infants. An indirect effect in mothers was not observed yet. Vaccine-driven selection pressure may have been responsible for the increase of non-typable isolates.

Laboratory investigations of vaccinated patients with varicella.

BACKGROUND: Accompanying varicella vaccination in children in Germany recommended with one (2004) and two (2009) doses, sentinel surveillance of varicella with a sample (n∼900) of private physicians was established in 2005. Physicians reported monthly aggregated data on all varicella cases and case-based on vaccinated patients, of whom skin lesion samples were laboratory investigated to identify varicella-zoster virus (VZV). We analyzed the impact of vaccination frequency on the number of cases and on laboratory results within the sentinel. METHODS: Swabs were obtained with a Teflon tip and sent together with a case-based questionnaire to the reference laboratory. VZV wild-type and vaccine-type was identified by polymerase chain-reaction (PCR) and pyrosequencing methods. Case-based data and laboratory results were analyzed descriptively. RESULTS: From April 2005 to March 2014, of all monthly reported cases (n=111,456) 4789 were vaccinated and eligible for further analysis. No differences were found between laboratory investigated and not investigated cases (1017 vs. 3772) except that the proportion of cases vaccinated twice was higher in lab-cases (29.4% vs. 16.1%). PCR remained negative in 69.6% (197/283) of breakthrough-cases vaccinated twice, in comparison to 22.7% (147/649) breakthrough-cases vaccinated once. VZV was confirmed in 500 (81) patients with breakthrough varicella after one (two) vaccination(s); identification of VZV wild-type, vaccine-type, or no further differentiation was possible in 485 (72), 5 (6), and 10 (3) cases, respectively. CONCLUSION: Varicella breakthrough disease is rare in Germany and suspected clinical cases require laboratory confirmation. The lower confirmation rate of VZV after two vaccine doses suggests a better protection compared to one dose.