The International Society for Vaccines is an organization that engages, supports, and sustains the professional goals of a diverse membership in all areas relevant to vaccines - 2018 ISV Annual Congress

Paper of the Month Jun 2018

Structural Characterization and Formulation Development of a Trivalent Equine Encephalitis Virus-like Particle Vaccine Candidate

J Pharm Sci. 2018 Jun 5. pii: S0022-3549(18)30327-7. DOI: 10.1016/j.xphs.2018.05.022 [Epub ahead of print]

Authors

VM Toprani, Y Cheng, N Wahome, H Khasa, LA Kueltzo, RM Schwartz, CR Middaugh, SB Joshi, DB Volkin

Affiliations

Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, USA

Vaccine Production Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, USA

Abstract

The zoonotic equine encephalitis viruses (EEV) can cause debilitating and life-threatening disease, leading to ongoing vaccine development efforts for an effective virus-like particle (VLP) vaccine based on three strains of EEV (Eastern, Western and Venezuelan or EEE, WEE and VEE VLPs, respectively). In this work, TEM and light scattering studies showed enveloped, spherical, and ∼70 nm sized VLPs. Biophysical studies demonstrated optimal VLP physical stability in the pH range of 7.5-8.5 and at temperatures below ∼50oC. Interestingly, the individual stability profiles differed notably between the three VLPs. Numerous pharmaceutical excipients were screened for their VLP stabilizing effects against thermal stress. Sucrose, sorbitol, sodium chloride and pluronic F-68 were identified as promising stabilizers and the concentrations and combinations of these additives were optimized. Candidate monovalent VLP bulk formulations were incubated at temperatures ranging from -80oC to 40oC to establish freeze-thaw, long-term (2-8°C) and accelerated stability trends. Good VLP stability was observed at each storage temperature, except for a distinct instability observed at -20°C. The interaction of monovalent and trivalent VLP formulations with aluminum adjuvants was examined, both in terms of antigen adsorption and desorption over time. The implications of these findings on future vaccine formulation development of EEV VLPs are discussed.

Paper of the Month May 2018

Acquisition of Virulence Genes by a Carrier Strain Gave Rise to the Ongoing Epidemics of Meningococcal Disease in West Africa

Proceedings of the National Acadamy of Sciences, U.S.A. https://doi.org/10.1073/pnas.1802298115

Authors

Ola Brønstad Brynildsrud, Vegard Eldholm, Jon Bohlin, Kennedy Uadiale, Stephen Obaro, and Dominique A. Cauganta

Affiliations

Division for Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway Nigeria Emergency Response Unit, Médecins sans Frontières, Sokoto, Nigeria Division of Pediatric Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA International Foundation Against Infectious Disease in Nigeria, Abuja, Nigeria WHO Collaborating Centre for Reference and Research on Meningococci, Norwegian Institute of Public Health, 0456 Oslo, Norway Department of Community Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway

Abstract

In the African meningitis belt, a region of sub-Saharan Africa comprising 22 countries from Senegal in the west to Ethiopia in the east, large epidemics of serogroup A meningococcal meningitis have occurred periodically. After gradual introduction from 2010 of mass vaccination with a monovalent meningococcal A conjugate vaccine, serogroup A epidemics have been eliminated. Starting in 2013, the northwestern part of Nigeria has been affected by yearly outbreaks of meningitis caused by a novel strain of serogroup C Neisseria meningitidis (NmC). In 2015, the strain spread to the neighboring country Niger, where it caused a severe epidemic. Following a relative calm in 2016, the largest ever recorded epidemic of NmC broke out in Nigeria in 2017. Here, we describe the recent evolution of this new outbreak strain and show how the acquisition of capsule genes and virulence factors by a strain previously circulating asymptomatically in the African population led to the emergence of a virulent pathogen. This study illustrates the power of long-read whole-genome sequencing, combined with Illumina sequencing, for high-resolution epidemiological investigations.

Paper of the Month Mar 2018

Sterile Protection Against Human Malaria by Chemoattenuated PfSPZ Vaccine

Nature. 2017 Feb 23;542(7642):445-449

Authors

Benjamin Mordmüller1, Güzin Surat1, Heimo Lagler1,2, Sumana Chakravarty3, Andrew S. Ishizuka4, Albert Lalremruata1, Markus Gmeiner1, Joseph J. Campo5, Meral Esen1, Adam J. Ruben3, Jana Held1, Carlos Lamsfus Calle1, Juliana B. Mengue1, Tamirat Gebru1, Javier Ibáñez1, Mihály Sulyok1, Eric R. James3, Peter F. Billingsley3, Natasha KC3,6, Anita Manoj3, Tooba Murshedkar3, Anusha Gunasekera3, Abraham G. Eappen3, Tao Li3, Richard E. Stafford3,6, Minglin Li3,6, Phil L. Felgner7, Robert A. Seder4, Thomas L. Richie3, B. Kim Lee Sim3,6, Stephen L. Hoffman3* & Peter G. Kremsner1*

Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany. Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, 1090 Vienna, Austria. Sanaria Inc., Rockville, Maryland 20850, USA. Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. Antigen Discovery Inc., Irvine, California 92618, USA. Protein Potential, LLC, Rockville, Maryland 20850, USA. Department of Medicine, University of California Irvine, Irvine, California 92697, USA.

Abstract

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drugresistant parasites1. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf ) sporozoites (PfSPZ) inoculated by mosquitoes2–4; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ (‘PfSPZ Vaccine’)5,6; or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine7–10 or mefloquine11 (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ (‘PfSPZ Challenge’12,13) to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZCVac) 14. Three doses of 5.12 × 104 PfSPZ of PfSPZ Challenge12,13 at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

Paper of the Month Apr 2018

Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies.

Cell. 2018 Apr 5;173(2):417-429.e10.

Authors

Chen YQ, Wohlbold TJ, Zheng NY, Huang M, Huang Y, Neu KE, Lee J, Wan H, Rojas KT, Kirkpatrick E, Henry C, Palm AE, Stamper CT, Lan LY, Topham DJ, Treanor J, Wrammert J, Ahmed R, Eichelberger MC, Georgiou G, Krammer F, Wilson PC.

Abstract

Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.

Paper of the Month Feb 2018

A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases.

J Infect Dis. 2018 Feb 28. doi: 10.1093/infdis/jiy103. [Epub ahead of print].

Authors

Erbelding EJ, Post D, Stemmy E, Roberts PC, Augustine AD, Ferguson S, Paules CI, Graham BS, Fauci AS.

Abstract

A priority for the National Institute of Allergy and Infectious Diseases (NIAID) is development of an influenza vaccine providing durable protection against multiple influenza strains, including those that may cause a pandemic, i.e., a universal influenza vaccine. To invigorate research efforts, NIAID developed a strategic plan focused on knowledge gaps in three major research areas, as well as additional resources required to ensure progress towards a universal influenza vaccine. NIAID will use this plan as a foundation for future investments in influenza research and will support and coordinate a consortium of multidisciplinary scientists focused on accelerating progress towards this goal.

Paper of the Month Jan 2018

The role of vaccines in preventing bacterial antimicrobial resistance.

Nat Med. 2018 Jan 9;24(1):10-19. doi: 10.1038/nm.4465. Review.

Authors

Jansen KU, Knirsch C, Anderson AS.

Abstract

Antimicrobial resistance (AMR) and the associated morbidity and mortality due to bacterial pathogens have been increasing globally to alarming levels. The World Health Organization (WHO) has called for global action on AMR, supported worldwide by governments, health ministries and health agencies. Many potential solutions to stem AMR are being discussed and implemented. These include increases in antimicrobial stewardship, investment in research and development to design new classes of antibiotics, and reduction of antibiotic use in rearing of livestock. However, vaccines as tools to reduce AMR have historically been under-recognized in these discussions, even though their effectiveness in reducing disease and AMR is well documented. This review article seeks to highlight the value of vaccines as an additional modality to combat AMR globally, using select examples. It also will provide perspectives on how vaccines could be more effectively used in this effort.