Next generation corona vaccines
To provide strong protection against variants of the SARS-CoV-2 coronavirus, to help immunocompromised people, and to prevent asymptomatic infections, companies and research groups are developing additional vaccines against Covid-19.
The Covid 19 pandemic continues unabated in large parts of the world. New variants of the pathogen, the SARS-CoV-2 coronavirus, continue to emerge, also known as mutants. They have slightly altered proteins, which in some cases makes them even more contagious. Fortunately, vaccination with the approved first-generation Covid-19 vaccines (developed against the original form of the virus) have also proven to be effective against most of these variants. But against some variants, such as variant beta and delta, protection is lower than against the original virus. And there is concern that other variants will emerge against which the current vaccines provide poor protection. This is currently being tested for the Omikron variant (see box).
Dr. Rolf Hömke, research spokesman for the vfa, answered questions from Radio Bremen Zwei presenter Kristin Hunfeld on 01 December 2021.
Topic: Virus variants and the efficacy of mRNA vaccines
You can listen to the conversation here:
According to studies, a simple way to further improve protection or prevent its weakening is to give an additional booster vaccination with one of the already approved vaccines. Accordingly, the first approvals for such injections, also known as "booster vaccinations", have been granted worldwide - in the EU for the vaccines from BioNTech/Pfizer and Moderna. A corresponding extension of the approval for Janssen's vaccine is currently under review.
However, modified or newly developed vaccines could be even more reliable. In addition, existing vaccines are not optimally effective in people with weakened immune systems, such as cancer patients undergoing chemotherapy. Therefore, many companies and research institutes are already working on second-generation vaccines, while others are still finishing their first-generation vaccines. Some are designed as booster vaccines, others as basic immunisation vaccines. A third goal for the development of second-generation vaccines is that they provide a strong immune response directly in the respiratory tract, so that the vaccination results in no one being able to "harbor" the virus (without getting sick themselves) and infect others.
The vfa provides information on the development and significance of the variants of the SARS-CoV-2 coronavirus here.
The following three tables show examples of projects already underway for vaccines that are intended to fulfil these goals (without claiming to be complete).
2nd generation vaccines in development to provide even better protection against variants
| Company, institute or consortium | Name of the vaccine | Vaccine type | Explanation | Development status(1) | |
| BioNTech/Pfizer (Germany / USA) | BNT162b2SA | monovalent mRNA vaccine | For a) booster vaccination with one injection for those previously vaccinated twice with the first BioNTech/Pfizer vaccine Comirnaty; and b) as first vaccination with two injections for those previously unvaccinated. Contains mRNA adapted to variant Beta. To be developed as a prototype for other variant-adapted vaccines. | Phase II/III | |
| Sanofi / GSK (France / UK) | tbd | monovalent protein-based vaccine with adjuvant | contains spike protein of the beta variant as antigen; to be tested a) as first vaccination and b) in lower doses as booster vaccination | Phase III since approx. 27.05.2021; initially, however, an antigen of the original SARS-CoV-2 is being tested; the study part with antigen of variant beta will follow later on | |
| Valneva (Austria) | VLA2101 | Vaccine based on inactivated complete SARS-CoV-2 viruses, with adjuvant from Dynavax | is optimized for an (unspecified) variant of SARS-CoV-2; being tested for first vaccination | Phase III since mid-August 2021 in New Zealand; being tested here in comparison with Valneva vaccine against the original SARS-CoV-2, with adults and adolescents 12 years and older | |
| Arcturus Therapeutics (USA) | ARCT-154 | Vaccine with self-amplifying RNA | adapted to the Delta variant and other Variants of Concern | Phase III in Vietnam | k. A. |
| Moderna (USA) | mRNA-1273.211 | bivalent mRNA vaccine | For booster vaccination with one injection for those previously vaccinated twice with the first Moderna vaccine. In addition to mRNA-1273 from the first Moderna vaccine, also contains mRNA-1273.351 adapted to the beta variant. | Phase II/III (for vaccines with one of each mRNA) | |
| AstraZeneca (UK) | AZD2816 | Vector virus vaccine | Vaccine with vector viruses containing a variant beta-adapted gene for spike protein. According to the manufacturer, the vaccine is otherwise identical to the already licensed vaccine Vaxzevria. Being tested as booster vaccine (with one injection) or as first vaccination (with two injections). | Phase II/III (in UK, South Africa, Brazil and Poland) | |
| BioNTech (Germany) | BNT162b2 | mRNA vaccine against SARS-CoV-2 Delta | Contains mRNA adapted to the Delta variant. Administered as a booster vaccine. | Phase II | |
| BioNTech (Germany) | BNT162b2 (B.1.1.7 + B.1.617.2) | mRNA vaccine against SARS-CoV-2 Delta | bivalent; contains mRNA adapted to variant alpha and variant delta. Administered as a booster vaccine. | Phase II | |
| BioNTech (Germany) | BNT162b2 (B.1.1.7) | mRNA vaccine against SARS-CoV-2 Delta | Contains mRNA adapted to variant alpha. Administered as a booster vaccine. | Phase II | |
| Gritstone bio (USA) | tbd | Vector virus vaccine (first injection) + mRNA vaccine (second injection) | Vaccines lead to the expression of other antigens besides the spike protein (including for the nucleocapsid); these in turn induce antibody and T-cell responses in vaccinated individuals. | Phase I | |
| Gritstone bio (USA) | GRT-R910 | mRNA vaccine with self-amplifying mRNA | leads to the expression of additional antigens besides the spike protein; these in turn induce antibody and T-cell response in vaccinated individuals. | Phase I (in UK) | |
| ImmunityBio (USA) | tbd | Vector virus vaccine | Leads to expression of spike and nucleocapsid protein of SARS-CoV-2; vector virus is hAd5 (which bypasses any immunity to adenoviruses); could be administered subcutaneously, orally or sublingually | Phase I (also Phase I/II/III trial approved in South Africa) | |
| OSE Immunotherapeutics (France) | CoVepiT | Peptide vaccine with different peptides (length: 8 to 11 amino acids) derived from 11 different proteins of SARS-CoV-2 | leads to stimulation of a T-cell response in vaccinated individuals, which also protects against viruses with mutated spike protein | Phase I | |
| Codagenix (USA) and Serum Institute of India | COVI-VAC | Vaccinewith live attenuated virus administered nasally | Vaccine contains all viral proteins, making it potentially effective against different variants of SARS-CoV-2 | Phase I | |
| Bavarian Nordic (R&D in Germany) and AdaptVac in the PREVENT-nCoV consortium | ABNCoV2 | protein-based vaccine with virus-like particles (cVLP) | Vaccine containing capsid virus-like particles (developed by AdaptVac) | Phase I (completed; Phase II in preparation) | |
| Novavax (USA) | SII B.1.251 (monovalent) | protein-based vaccine with antigen from the beta variant (genetically engineered, in nanoparticles) with adjuvant Matrix-M1; monovalent | being tested with previously unvaccinated patients | Phase I/II | |
| Novavax (USA) | SII Bivalent | protein-based vaccine with antigens from the original SARS-CoV-2 and the beta variant (genetically engineered, in nanoparticles) with adjuvant Matrix-M1 | Being tested with previously unvaccinated patients | Phase I/II | |
| Novavax (USA) | SII B.1.617.2 (monovalent) | protein-based vaccine with antigen from the delta variant (genetically engineered, in nanoparticles) with adjuvant Matrix-M1; monovalent | being tested with previously unvaccinated patients | Phase I/II | |
| CureVac/GSK (Germany / UK) | CV2CoV | Multivalent mRNA vaccine with modified mRNA molecular structure (compare with CVnCoV) | Antibodies induced in animal experiments also neutralize variants alpha and beta as well as B.1.1.298. The structure of the mRNA molecules was optimized for increased and prolonged protein expression in the cells, which might allow lower dosing. Multiple variant-adapted mRNAs are planned to be combined in a vaccine. | preclinical development | |
| Prime Vector Technologies (Germany) | tbd | Vector virus vaccine based on parapox virus | Vaccine provides for expression of multiple antigens. | preclinical development | |
| Osivax (France) | OVX-CoV | protein-based vaccine | Vaccine contains antigenic heptamers with complementary structures (positively charged poly-Arg tails) that promote uptake into certain immune cells and indirect formation of cytotoxic T cells; antigen is derived from nucleocapsid protein, which is similar in SARS, SARS-CoV-2, and MERS; therefore, vaccine may protect against all coronaviruses. | Preclinical Develop. | |
| Ziphius Vaccines and Ghent University (Belgium / Belgium) | ZIP-1642 | mRNA vaccine | self-amplifying mRNA for multiple antigens, in lipid nanoparticles | preclinical development | |
| University of Würzburg / Aeterna Zentaris (Germany / USA) | tbd | Oral vaccination with genetically modified, live typhoid vaccine bacteria | Bacteria carry two different proteins of SARS-CoV-2 after genetic modification | preclinical development | |
| baseclick (Germany) | tbd | mRNA vaccine | mRNA contains gene sequence for the nucleocapsid protein of SARS-CoV-2, not the mutation-prone spike protein; it is coupled with sugar molecules and not formulated with lipids | Preclinical Develop. | |
| Sorrento Therapeutics (USA) | tbd | multivalent mRNA vaccine | with several mRNAs coding for different spike variants, including delta and lambda; for i.m. injection or needle-free application into a lymph node | preclinical development | |
| ReiThera (Italy) | tbd | Vector virus vaccines against SARS-CoV-2 variants based on GRAd vector technology (using an adenovirus from gorillas) | Details are not yet published. The project is funded by the Bill & Melinda Gates Foundation. The vaccines will primarily benefit developing and emerging countries. | Laboratory stage |
(1) Phase I, II and III refers to the phases of testing with volunteers in clinical trials
Sources: Research by the vfa, press statements by the companies mentioned, WHO
Vaccines of the 2nd generation in development, which are to protect especially immunosuppressed persons
| Company, institute or consortium | Name of the vaccine | Vaccine type | Explanation | Development status |
| City of Hope (USA) | COH04S1 | Vector virus vaccine based on the MVA virus | contains genes for spike and nucleocapsid protein of SARS-CoV-2 | Phase II |
| University of Tübingen | CoVac-1 | Peptide-based vaccine | Vaccine specifically for cancer patients undergoing chemotherapy and other immunocompromised individuals. Contains peptides that specifically activate the T-cells of the immune system to fight SARS-CoV-2. | Phase II |
| Emergex Vaccines (UK) | tbd | Peptide-based vaccine | Vaccinecontains peptides specifically designed to activate immune system T cells (CD8+ cells) to fight SARS-CoV-2 and SARS-CoV-1. However, the company does not explicitly target immunocompromised patients. Vaccine is to be applied intradermally with microcannulas. | preclin. Development (Phase I study approved in Switzerland) |
| German Center for Infection Research / Hannover Medical School / IDT Biologika (Germany) | tbd | Vaccine for inhalation | Vector virus vaccine based on MVA viruses; intended primarily for immunocompromised individuals | preclinical development, Phase I trial pending |
Sources: Research by the vfa, press statements by the institutes mentioned, WHO
2nd generation vaccines in development to prevent vaccinated persons from being carriers without symptoms
| Company, institute or consortium | Name of the vaccine | Vaccine type | Explanation | Development status |
| University of Hong Kong, Xiamen University and Beijing Wantai Biological Pharmacy (China). | DelNS1-2019-nCoV-RBD-OPT1 | Intranasal vector virus vaccine | Vector virus vaccine based on an attenuated influenza virus with the receptor binding domain of SARS-CoV-2. | Phase III |
| Bharat Biotech (India), Precision Virologics (USA) and Washington University School of Medicine in St Louis (USA) | BBV154 | intranasal vector virus vaccine | Vector viruses based on a chimpanzee adenovirus not capable of replication | Phase II |
| Center for Genetic Engineering and Biotechnology (Cuba) | CIBG-669 | nasal-applied protein-based vaccine | with receptor-binding domain as antigen; the antigen is also contained in the Cuban injection vaccine "Abdala", which is already being tested in Phase III | Phase I/II |
| University of Oxford | ChAdOx1-S | intranasal vector virus vaccine | Vector viruses based on a chimpanzee adenovirus not capable of replication | Phase I |
| Altimmune (USA) | AdCOVID | intranasal vector virus vaccine | Vector viruses based on adenovirus 5 that is not capable of replication | Phase I |
| Meissa Vaccines (USA) | MV-014-212 | intranasal vector virus vaccine | based on an attenuated virus RSV | Phase I |
| Codagenix (USA) and Serum Institute of India | COVI-VAC | intranasal vaccine | contains attenuated SARS-CoV-2 viruses that cannot cause the disease | Phase I |
| CyanVac (USA) | CVXGA1 | intranasal vector virus vaccine | Contains attenuated parainfluenza 5 viruses with the gene for the spike protein of SARS-CoV-2 as vector viruses | Phase I in the USA |
| Gamaleya Institute (Moscow, Russia) | tbd | Nasal spray vaccine with vector viruses | Vector viruses based on an adenovirus; they are the same as in the booster injection of the vaccine Sputnik V | preclinical development(in preparation: phase II) |
| Oragenics (USA) | Terra Co-2 | intranasal protein-based vaccine with adjuvant BDX-300 | with adjuvant BDX-300/301 | preclinical development |
| Consortium vir4vac (Germany) | tbd | Nasal spray vaccine with vector viruses | based on Sendai viruses not capable of replication | Research phase |
Sources: Research by the vfa, Science 2021, press statements by the companies mentioned, WHO
Pandemic Preparedness Partnership
The Pandemic Preparedness Partnership - an alliance of various organisations, foundations and numerous pharmaceutical and diagnostics companies under the leadership of the British government's science advisor - also aims to enable vaccine development against a new pathogen or a SARS-CoV-2 variant with new pandemic potential within 100 days in a few years. This was reiterated at a G7 event in Oxford (UK) on 04.06.2021.
