COVID Vaccines: What’s Available Now and What’s in the Works?

It has been more than a year since the World Health Organization (WHO) and the U.S. Department of Health and Human Services (HHS) declared the end of the COVID-19 pandemic, but COVID-19 vaccines are still prominent in the preventive healthcare space.¹ “COVID-19 is here to stay, and the world will continue to need tools to prevent it, test for it and treat it,” says Tedros Adhanom Ghebreyesus, director-general of WHO.²

According to WHO and HHS, “While clinical and real-world data still show that existing COVID-19 vaccine options can help protect against the virus, we are continuing to follow the science by exploring new vaccine approaches that may be needed as the virus evolves.”¹ Indeed, not only are vaccine manufacturers still making COVID-19 vaccines to prevent the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), but they are now making next-generation and combination vaccines that prevent the ever-mutating SARS-CoV-2 virus, as well as other respiratory viruses such as seasonal influenza and respiratory syncytial virus (RSV).

Following are the currently available COVID-19 vaccines and a look at what is in the works from three of the top 10 global vaccine manufacturers.

Pfizer-BioNTech

Pfizer-BioNTech’s current COVID-19 vaccine — COMIRNATY 2023-2024 Formulation — is an updated vaccine tailored to the SARS-CoV-2 XBB.1.5 sublineage, and is indicated as a single dose for individuals 5 years of age and older.

Preclinical data showed this updated COVID-19 vaccine generated improved neutralizing antibody responses against multiple circulating Omicron-related sublineages, including XBB.1.5, BA.2.86 (Pirola) and EG.5.1 (Eris). Data from real-world studies complement the Phase III clinical trial data and provide additional evidence that the vaccine provides effective protection against severe disease. The companies’ COVID-19 vaccine differs from its earlier COVID-19 vaccines only in that it contains messenger RNA (mRNA) coding for the spike protein of a different SARS-CoV-2 sublineage.

The U.S. Food and Drug Administration’s (FDA) approval of Pfizer-BioNTech’s updated COMIRNATY vaccine was based on the full body of previous clinical, preclinical and real-world evidence supporting the safety and efficacy of the companies’ COVID-19 vaccines. The companies’ FDA application included preclinical data showing improved responses against multiple Omicron XBB sublineages, including XBB.1.5, XBB.1.16 and XBB.2.3, compared to the Omicron BA.4/BA.5-adapted bivalent vaccine.

The Pfizer-BioNTech collaboration is currently working on an mRNA-based combination vaccine for COVID-19 and influenza. Based on positive results from a Phase I/II clinical trial among healthy adults 18 to 64 years of age, the vaccine candidate showed robust immunogenicity against all targeted influenza and SARS-CoV-2 strains. The vaccine candidates were compared to a licensed influenza vaccine and the companies’ Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine given at the same visit.

Data from this clinical trial showed the companies’ lead formulations demonstrated robust immune responses to influenza A, influenza B and SARS-CoV-2 strains. Pfizer-BioNTech plan to start a Phase III trial soon. The companies have also received fast track designation from FDA for this vaccine.

With its robust vaccine pipeline, Pfizer says it aims to deliver multiple innovative vaccines in the near future. “We have an ambitious and comprehensive program exploring combination vaccines for multiple respiratory viruses including COVID-19, respiratory syncytial virus and influenza,” said a Pfizer spokesperson.

Pfizer-BioNTech’s COMIRNATY vaccine is based on the companies’ proprietary mRNA technology. The versatile and flexible mRNA technology is a molecule that contains the instructions that direct the cells to make a protein using its natural machinery. mRNA-based vaccines have demonstrated their ability to induce robust antibody and T-cell responses. “mRNA is likely to be at least one of the waves of the future for vaccines. Overall, it is a very powerful technique to be able to create a lot of a vaccine fast,” explained a Pfizer spokesperson. “The benefit is that the technology is very adaptable. We can potentially go in and change the mRNA in the formulation to target a new antigen, and we can make a lot of high-quality vaccine material relatively quickly. We utilize the mRNA platform for vaccine targets, which gives us the flexibility to explore combinations of different vaccine modalities for COVID-19, influenza, varicella zoster virus and combinations.”

Unlike conventional vaccines — which can take many months or even years to cultivate — mRNA vaccines can be developed quickly using the pathogen’s genetic code. By having the vaccine recipient make the antigen via the instructions encoded in the mRNA, the antigen can look more like it does during a live infection versus when engineered in a laboratory or produced in eggs, which may improve protection.

“We are encouraged by early results in our Phase I/II study of our combination vaccine candidates against COVID-19 and influenza. This vaccine has the potential to lessen the impact of two respiratory diseases with a single injection and may simplify immunization practices for providers, patients and healthcare systems all over the world. mRNA-based vaccines have demonstrated their ability to induce robust antibody and T-cell responses, and we look forward to starting Phase III clinical development. This is an important achievement toward our ambition of providing a broad portfolio of respiratory combination vaccines,” said Annaliesa Anderson, PhD, senior vice president and head of vaccine research and development at Pfizer. 

Moderna

Moderna’s current COVID-19 vaccine is Spikevax, which uses its proprietary mRNA technology platform. In June 2023, FDA advised that COVID-19 vaccines should be updated to a monovalent XBB.1.5 composition for the 2023-2024 vaccination season. At the June Vaccines and Related Biological Products Advisory Committee meeting, Moderna presented clinical data showing that its updated Spikevax vaccine resulted in robust immune responses across multiple XBB sublineages, including XBB.1.5 and XBB.1.16.

In September 2023, Moderna announced that FDA had approved its supplemental biologics license application (sBLA) for Spikevax for ages 12 years and older. Emergency use authorization (EUA) for Spikevax was also received by FDA for individuals 6 months through 11 years of age. Moderna’s updated COVID-19 vaccine contains spike proteins for the XBB.1.5 sublineage of SARS-CoV-2 to help prevent COVID-19 in individuals 6 months of age and older.

The Centers for Disease Control and Prevention (CDC) says people who were vaccinated with Moderna’s updated COVID-19 vaccine, which includes a component that corresponds to the XBB lineage of the Omicron variant, showed a strong immune response against some of the variants that are common now such as XBB.1.5, EG.5.1 and FL.1.5.1. They also had an overall boost in COVID-19 immunity that may have waned since their last vaccination or infection. Their antibody responses after vaccination were about 17 times higher against XBB 1.5 and about 10 times higher against BA.2.86 (a rare new variant) compared to before vaccination. CDC also says these data signal that the updated 2023-2024 COVID-19 vaccine likely provided strong protection against COVID-19 during the 2023-2024 virus season.³

Moderna says its upcoming Spikevax vaccines would be determined by strain selection in Spring 2024, which is set by regulatory authorities, for the 2024-2025 vaccination season.

Moderna is currently working on two new types of COVID-19 vaccines. Its next-generation COVID-19 vaccine is a refrigerator-stable (mRNA-1283) vaccine that is currently in its pivotal Phase III study. The company anticipates data from the study in the first half of 2024.

Moderna is also working on a seasonal flu plus COVID combination vaccine (mRNA-1083). Its Phase III trial of this combination vaccine is fully enrolled. The company anticipates data from the study in 2024.

“COVID-19 remains a leading cause of death in the U.S. and poses a significant threat to vulnerable populations. As the primary circulating strain continues to evolve, updated vaccines will be critical to protecting the population,” said Stéphane Bancel, CEO of Moderna.⁴

Novavax

Novavax’s current COVID-19 vaccine is the Novavax COVID-19 Vaccine (its commercial name is not yet approved for use in the U.S.), adjuvanted (2023-2024) Formula (NVX-CoV2601), for use in individuals 12 years and older. The vaccine is under FDA EUA, and it is recommended by CDC. Currently, the company is working toward full BLA. Novavax’s COVID-19 vaccine is the only protein-based, non-mRNA COVID-19 vaccine option available in the U.S.

Non-clinical data showed that Novavax’s COVID-19 vaccine induced functional immune responses against XBB.1.5, XBB.1.16 and XBB.2.3 variants. Additional non-clinical data demonstrated Novavax’s vaccine induced neutralizing antibody responses to newly emerging subvariants JN.1, BA.2.86, EG.5.1, FL.1.5.1 and XBB.1.16.6, as well as robust CD4+ polyfunctional cellular (T-cell) responses against EG.5.1 and XBB.1.16.6. These data indicate Novavax’s vaccine can stimulate both arms of the immune system and may induce a broad response against currently circulating variants. 

The latest updated Novavax COVID-19 vaccine targets the XBB subvariants. Additional non-clinical data has demonstrated that this vaccine-induced neutralizing antibody responds to subvariant JN.1 in addition to the previous variants.

Novavax uses adjuvanted protein-based technology to develop vaccines, which combines the power and speed of genetic engineering to efficiently produce protein-based nanoparticles. These protein-based nanoparticles work with Novavax’s propriety Matrix-M adjuvant, which helps to enhance immunogenicity. The Matrix-M adjuvant comes from saponins, naturally occurring compounds in the bark of the Quillaja Saponaria (soapbark) tree, commonly found in Chile. This adjuvant is a key element in the company’s technology platform. When saponins are mixed with Novavax’s vaccine nanoparticles, the combination of ingredients has been shown to enhance the immune system response to the company’s vaccines.

Novavax’s vaccine technology is disease-agnostic and adaptable. As the SARS-CoV-2 virus evolves, the vaccine can be adjusted to use the version of the spike protein found in new variants. Therefore, if a new SARS-CoV-2 variant appears and Novavax’s COVID-19 vaccine does not provide sufficient protection, the genetic sequence of the new variant is used to produce a new version of the recombinant spike protein.

Novavax is currently working on combining more than one type of protein-based nanoparticle into a single vaccine candidate to help provide coverage for two or more strains of the same virus. The company’s nanoparticle technology is now also being used to combine antigens from different pathogens to help immunize against more than one disease with a single vaccine. For example, Novavax is studying the combination of seasonal influenza with SARS-CoV-2, which may allow protection for individuals against influenza and COVID-19 through a single vaccine. According to the company, data from preclinical trials in animals have shown that a single shot of the combined vaccine successfully generated antibodies against both viruses at comparable levels to using either vaccine alone.

Novavax announced positive data from a Phase I/II clinical trial that evaluated the safety and immunogenicity of this investigational combination vaccine, which supported the advance and development of this candidate into its Phase III trial. Novavax expects to initiate the Phase III trial in the second half of 2024.

Robert Walker, MD, vice president and chief medical officer of Novavax, said, “Vaccination is one of the most cost-effective preventive health investments we can make as an industry and a society. As I look to 2024, I am excited to see years of innovation and hard work on the development of new vaccines pay off even more with a profound impact on public health.”

Looking Forward

These three global vaccine manufacturers are continuing their work on novel vaccines for new strains of the SARS-CoV-2 virus, as well as next-generation and combination vaccines to ensure the population has the right vaccine at the right time to prevent serious illness or death from SARS-CoV-2 and other respiratory viruses.