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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591001

2. INTRODUCTION

The BNT162 RNA-based COVID-19 vaccines are currently being investigated for
prevention of COVID-19 in healthy individuals.

2.1. Study Rationale
The purpose of the study is to rapidly describe the safety, tolerability, and immunogenicity of
2 BNT162 RNA-based COVID-19 vaccine candidates against COVID-19, and the efficacy
of 1 candidate, in healthy individuals. There are currently no licensed vaccines to prevent
infection with SARS-CoV-2 or COVID-19. Given the global crisis of COVID-19 and fast
expansion of the disease in the United States and elsewhere, the rapid development of an
effective vaccine is of utmost importance.

2.2. Background

In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.
In January 2020, it became clear that a novel coronavirus (2019-nCoV) was the underlying
cause. Later in January, the genetic sequence of the 2019-nCoV became available to the
World Health Organization (WHO) and public (MN908947.3), and the virus was categorized
in the Betacoronavirus subfamily. By sequence analysis, the phylogenetic tree revealed a
closer relationship to severe acute respiratory syndrome (SARS) virus isolates than to another
coronavirus infecting humans, the Middle East respiratory syndrome (MERS) virus.

SARS-CoV-2 infections and the resulting disease, COVID-19, have spread globally,
affecting a growing number of countries.

1
On 11 March 2020, the WHO characterized the COVID-19 outbreak as a pandemic.
The WHO Situation Update Report dated 30 March 2020 noted 693,224 confirmed cases
with 33,106 deaths globally, including 142,081 confirmed cases with 2457 deaths in the
2
Americas. The United States currently has the most reported cases globally. At the time of
this communication, the number of confirmed cases continues to rise globally. There are
currently no vaccines or effective antiviral drugs to treat SARS-CoV-2 infections or the
3
disease it causes, COVID-19.
A prophylactic, RNA-based SARS-CoV-2 vaccine provides one of the most flexible and
4,5
fastest approaches available to immunize against the emerging virus.

The development of an RNA-based vaccine encoding a viral antigen, which is then expressed
by the vaccine recipient as a protein capable of eliciting protective immune responses,
provides significant advantages over more traditional vaccine approaches. Unlike live
attenuated vaccines, RNA vaccines do not carry the risks associated with infection and may
be given to people who cannot be administered live virus (eg, pregnant women and
immunocompromised persons). RNA-based vaccines are manufactured via a cell-free in
vitro transcription process, which allows an easy and rapid production and the prospect of
producing high numbers of vaccination doses within a shorter time period than achieved with
traditional vaccine approaches. This capability is pivotal to enable the most effective
response in outbreak scenarios.

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