SPP2

The week began with positive updates in the vaccine development space against various infectious diseases, including pneumococcal disease, SARS-CoV-2 and a chikungunya virus-like illness. BioSpace highlights four of these below. Emergent's Chikungunya Virus-Like Particle Vaccine Emergent BioSolutions published two-year data from its Phase II clinical trial on the immunogenicity and safety of the PXVX0317 vaccine when used on chikungunya virus virus-like particle (CHIKV VLP) naive adults in the United States. The study, which involved 415 participants, achieved the primary endpoint of geometric mean titer of anti-CHIKV neutralizing antibody on day 57. The vaccine was found to be well-tolerated and induce a durable serum neutralizing antibody response versus the chikungunya virus for up to two years. CHIKV affects people in over 100 countries and spreads through infected mosquito bites. Symptoms include joint and muscle pain, headache, fever, rashes and joint swelling. Details are available online in The Lancet Infectious Diseases journal. Merck's Pneumococcal Vaccine Hits Primary immunogenicity Targets Merck announced favorable results from the Phase I/II study of V116-001, its investigational 21-valent pneumococcal conjugate vaccine. The trial is assessing the vaccine's tolerability, safety and immunogenicity in two age groups: 18 to 49 for Phase I and 50-plus for Phase II. V116-001 was observed to be well-tolerated and had met primary immunogenicity goals, with researchers comparing its impact to the current market player Pneumovax 23. Responses were observed 30 days after the vaccine was given. The vaccine received Breakthrough Therapy designation in early 2022 from the U.S. Food and Drug Administration to prevent invasive pneumococcal disease (IPD) and pneumococcal pneumonia from 21 Streptococcus pneumoniae serotypes in adults ages 18 and up. "Consistent with our portfolio strategy, V116 is designed to specifically target serotypes that are responsible for 85 percent of all invasive pneumococcal disease in individuals aged 65 and over in the United States as of 2019," Dr. Eiav Barr, SVP and chief medical officer at Merck Research Laboratories noted. Affinivax Leverages MAPS Platform Against Pneumococcal Disease Affinivax announced positive preclinical data from its study evaluating whether incorporating novel pneumococcal fusion protein SPP2 with its vaccine candidate AFX3772 would deliver enhanced protection versus serotype 3 invasive pneumococcal disease. The company utilized its MAPS technology platform to engineer a multivalent vaccine by affinity-linking antigens from the target pathogen Streptococcus pneumoniae. SPP2 was added into a MAPS vaccine candidate with more than 30 serotypes, thus creating highly potent antibodies against the toxin. Testing on mouse models, researchers observed that protection was only achieved by those that were given the MAPS vaccine candidate. "The MAPS platform offers the possibility of engineering next generation pneumococcal vaccines that can be broadly effective against Streptococcus pneumoniae. These data strongly support a vaccine approach that includes both pneumococcal polysaccharides and conserved pneumococcal proteins to overcome the resistance of serotype 3 to traditional conjugate vaccines," Gilles Besin, Ph.D., vice president and head of discovery research at Affinivax stated. Results will be presented at the 12th International Symposium on Pneumococci and Pneumococcal Diseases, June 19 to 23 in Toronto. Ocugen and Bharat Biotech's COVID-19 Vaccine Shines in Children Ocugen announced positive pediatric Phase II/III study results for its COVID-19 vaccine Covaxin (BBV152) in children ages 2 to 18. Covaxin, developed alongside partner Bharat Biotech International, was being evaluated for reactogenicity and immunogenicity. "We have now achieved our goal of developing a safe and efficacious COVID-19 vaccine for adults and children, for primary immunization and booster doses, making Covaxin a universal vaccine. It has proven to be a highly safe vaccine based on data from more than 50 million doses administered to children in India," Dr. Krishna Ella, chairman and managing director of Bharat Biotech, commented. The open-label, non-randomized trial was conducted in six hospitals in India and involved 526 healthy children. Details of the study are published in The Lancet Infectious Diseases. Covaxin so far has an emergency use listing from the World Health Organization. It can be given to adults and children alike.

June 21, 2022 11:00 UTC – Preclinical data show synergistic protective effect of anti-protein and anti-polysaccharide antibodies in a highly virulent model of serotype 3 invasive pneumococcal disease – – Presentation at the 12th International Symposium on Pneumococci and Pneumococcal Diseases – CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Affinivax, Inc. (“Affinivax”), a clinical stage biopharmaceutical company pioneering the development of a novel class of vaccines with its MAPS™ (Multiple Antigen Presenting System) platform, announced the company is presenting preclinical data demonstrating that a next generation pneumococcal vaccine candidate incorporating a novel pneumococcal fusion protein conferred enhanced protection in a highly virulent model of serotype 3 invasive pneumococcal disease, at the 12th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-12) taking place on June 19-23 in Toronto. “The continued threat of Streptococcus pneumoniae in both the developed and developing world requires further innovation and novel strategies to provide enhanced protection against this pathogen,” said Rick Malley, MD, Chief Scientific Officer and Scientific Founder of Affinivax. “Serotype 3, in particular, has proven resistant to the effects of traditional conjugate vaccines. These new data presented by Affinivax reveal that the inclusion of a new conserved pneumococcal fusion protein using our versatile MAPS technology has the potential for next generation MAPS pneumococcal vaccines to enable enhanced protection against this serotype and provide broader coverage to patients.” Streptococcus pneumoniae causes pneumonia, bacteremia and meningitis, especially in infant and older adult populations. Over 100 different serotypes, characterized by diverse capsular polysaccharides (CPS) which surround the pneumococcal bacterium, have been identified. Serotype 3, a major cause of morbidity and mortality worldwide, is a serotype resistant to anti-CPS antibody-mediated protection; the incidence rates of serotype 3 invasive pneumococcal disease have not significantly declined following the introduction of 13-valent pneumococcal conjugate vaccines1. Highlights from the poster presentation, entitled “Synergistic protective effect of antibodies against polysaccharide type 3 and pneumococcal proteins in a highly virulent type 3 invasive disease model in mice,” are as follows: The MAPS technology platform enabled flexible engineering of a multivalent vaccine by affinity-linking protein antigens from the target pathogen, Streptococcus pneumoniae, to a backbone of pneumococcal polysaccharides. In the study, the novel fusion protein antigen SPP2, which includes a pneumolysin toxoid, was incorporated in a pneumococcal MAPS vaccine candidate containing over 30 different serotypes, resulting in the generation of highly potent, neutralizing antibodies to the toxin. A highly lethal type 3 pneumococcal invasive disease model was developed to evaluate whether antibodies to the SPP2 protein provide enhanced protection. In an active immunization model, three groups of mice were immunized with either: the traditional conjugate vaccine, Prevnar 13® (PCV13) alone, the fusion protein antigen SPP2 alone, or the combination of PCV13 and SPP2. Protection against serotype 3 invasive pneumococcal disease was only seen in the latter group. In a passive immunization model, in which mice received antibodies generated from PCV13 or a 30+ valent MAPS vaccine candidate containing CPS3 and SPP2, protection against serotype 3 invasive pneumococcal disease was only achieved with the MAPS vaccine candidate, even though the amounts of CPS3 antibodies were matched between the two groups. These data indicate that SPP2 confers synergistic protection in a serotype 3 invasive pneumococcal disease model, where traditional conjugate vaccines fail. “These data strongly support a vaccine approach that includes both pneumococcal polysaccharides and conserved pneumococcal proteins to overcome the resistance of serotype 3 to traditional conjugate vaccines,” said Gilles Besin, PhD, Vice President and Head of Discovery Research at Affinivax. “The MAPS platform offers the possibility of engineering next generation pneumococcal vaccines that can be broadly effective against Streptococcus pneumoniae.” Affinivax’s lead MAPS pneumococcal vaccine candidate is AFX3772, which has successfully completed a Phase 2 study in older adults, with a current clinical study in toddlers and planned study in infants. AFX3772 includes 24 pneumococcal polysaccharides as well as two conserved pneumococcal proteins, and has been shown in clinical studies to elicit both B-cell (antibody) and T-cell immunity against 24 Streptococcus pneumoniae serotypes. The MAPS technology platform enables the inclusion of additional pneumococcal polysaccharides and conserved pneumococcal proteins into next generation MAPS pneumococcal vaccines. About Affinivax, Inc. Affinivax is a clinical stage biopharmaceutical company pioneering the development of a novel class of vaccines designed to induce a broad and robust protective immune response to both disease-relevant polysaccharides and disease-relevant proteins in a single vaccine. Affinivax designs each of its vaccine candidates to optimize the protective immune response to one or both of these antigens utilizing the distinctive plug-and-play nature of its proprietary MAPS™ technology platform, presenting the potential opportunity to make a significant step forward in addressing major healthcare challenges posed by novel and resistant infectious diseases. Affinivax was founded in 2014 with an exclusive license to the MAPS™ technology from Boston Children’s Hospital. For more information, visit . 1 “Sugar-Coated Killer: Serotype 3 Pneumococcal Disease,” Front. Cell. Infect. Microbiol., December 23, 2020. Prevnar 13® is a registered trademark of Pfizer, Inc.